{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRhoC is emerging as a critical regulator of cancer progression, playing distinct roles in the control of cell morphology, migration, invasion, and metastasis across a diverse range of tumor types. Studies have shown that, unlike its closely related isoform RhoA, RhoC promotes polarized migration by restricting the lateral broadening of lamellipodia via effectors such as FMNL3, and its depletion leads to altered Rac1 activity and increased cell spreading (see, for example, the work in aggressive breast, ovarian, head and neck, and pancreatic carcinomas). Up‐regulation of RhoC has been correlated with advanced tumor stage, increased metastatic potential, and poorer clinical outcome in cancers such as inflammatory breast cancer, ovarian carcinoma, and hepatocellular carcinoma. Moreover, specific knockdown of RhoC by siRNA approaches in multiple tumor models markedly inhibited invasion, anchorage‐independent growth, angiogenesis, and metastasis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "25"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAt the molecular level, RhoC function is tightly controlled by its selective interactions with regulators and effectors that distinguish it from other Rho isoforms. For instance, dedicated guanine nucleotide exchange factors (GEFs) like SmgGDS and regulatory proteins such as IQGAP1 and Myo-GEF have been shown to preferentially modulate RhoC activity, while unique residues in RhoC help confer specificity against exchange by proteins like XPLN. In addition, RhoC is subject to regulation by microRNAs (for example, miR-10b, miR-138, and miR-372) and by post-translational modifications such as Akt1-mediated phosphorylation or p38γ-dependent ubiquitination modulation, which further fine-tune its ability to orchestrate actin-cytoskeletal rearrangements and downstream signaling cascades (including those involving FAK, MAPK, and Akt). Furthermore, cross-talk with pathways such as Notch signaling and potential modulation by viral oncogenes underline the complexity of its regulation, while studies of lncRNA expression and of syndecan interactions hint at additional layers of control."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "26", "end_ref": "39"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nThe therapeutic implications of targeting RhoC have also garnered considerable interest. Owing to its central role in regulating invasive and metastatic behaviors, interference with RhoC expression or its downstream signaling—through direct siRNA-mediated knockdown or modulation of its regulatory networks—has been shown to suppress metastasis and may diminish the cancer stem cell traits that contribute to treatment resistance. Such approaches not only impair cell motility and angiogenesis but also enhance susceptibility to therapies that induce DNA damage, highlighting RhoC as an attractive target for novel anti-metastatic strategies."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "40", "end_ref": "42"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Francisco M Vega, Gilbert Fruhwirth, Tony Ng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RhoA and RhoC have distinct roles in migration and invasion by acting through different targets."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biol (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1083/jcb.201011038"}], "href": "https://doi.org/10.1083/jcb.201011038"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21576392"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21576392"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "J-Y Pillé, C Denoyelle, J Varet, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Anti-RhoA and anti-RhoC siRNAs inhibit the proliferation and invasiveness of MDA-MB-231 breast cancer cells in vitro and in vivo."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Ther (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ymthe.2004.08.029"}], "href": "https://doi.org/10.1016/j.ymthe.2004.08.029"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15668138"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15668138"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Akiko Horiuchi, Tsutomu Imai, Cuiju Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Up-regulation of small GTPases, RhoA and RhoC, is associated with tumor progression in ovarian carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Lab Invest (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/01.lab.0000073128.16098.31"}], "href": "https://doi.org/10.1097/01.lab.0000073128.16098.31"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12808121"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12808121"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Celina G Kleer, Kenneth L van Golen, Yanhong Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Characterization of RhoC expression in benign and malignant breast disease: a potential new marker for small breast carcinomas with metastatic ability."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Pathol (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/S0002-9440(10)64877-8"}], "href": "https://doi.org/10.1016/S0002-9440(10"}, {"type": "t", "text": "64877-8) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11839578"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11839578"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Lu Jiang, Xiqiang Liu, Antonia Kolokythas, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Downregulation of the Rho GTPase signaling pathway is involved in the microRNA-138-mediated inhibition of cell migration and invasion in tongue squamous cell carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Cancer (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ijc.25320"}], "href": "https://doi.org/10.1002/ijc.25320"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20232393"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20232393"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "A J Ridley "}, {"type": "b", "children": [{"type": "t", "text": "RhoA, RhoB and RhoC have different roles in cancer cell migration."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Microsc (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/jmi.12025"}], "href": "https://doi.org/10.1111/jmi.12025"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23488932"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23488932"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Zhuo Liu, Jiaming Zhu, Hong Cao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "miR-10b promotes cell invasion through RhoC-AKT signaling pathway by targeting HOXD10 in gastric cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Oncol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/ijo.2012.1342"}], "href": "https://doi.org/10.3892/ijo.2012.1342"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22293682"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22293682"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Megumi Iiizumi, Sucharita Bandyopadhyay, Sudha K Pai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RhoC promotes metastasis via activation of the Pyk2 pathway in prostate cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/0008-5472.CAN-07-6700"}], "href": "https://doi.org/10.1158/0008-5472.CAN-07-6700"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18794150"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18794150"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Kenneth L van Golen, Li Wei Bao, Quintin Pan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mitogen activated protein kinase pathway is involved in RhoC GTPase induced motility, invasion and angiogenesis in inflammatory breast cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Exp Metastasis (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1023/a:1015518114931"}], "href": "https://doi.org/10.1023/a:1015518114931"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12090470"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12090470"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Min Lin, Melinda M DiVito, Sofia D Merajver, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulation of pancreatic cancer cell migration and invasion by RhoC GTPase and caveolin-1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cancer (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/1476-4598-4-21"}], "href": "https://doi.org/10.1186/1476-4598-4-21"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15969750"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15969750"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "F Xing, S Sharma, Y Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "miR-509 suppresses brain metastasis of breast cancer cells by modulating RhoC and TNF-α."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/onc.2014.412"}], "href": "https://doi.org/10.1038/onc.2014.412"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25659578"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25659578"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Quintin Pan, Li Wei Bao, Theodoros N Teknos, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Targeted disruption of protein kinase C epsilon reduces cell invasion and motility through inactivation of RhoA and RhoC GTPases in head and neck squamous cell carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/0008-5472.CAN-06-2646"}], "href": "https://doi.org/10.1158/0008-5472.CAN-06-2646"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17018591"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17018591"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Lei Wang, Linda Yang, Yongneng Luo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A novel strategy for specifically down-regulating individual Rho GTPase activity in tumor cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M308929200"}], "href": "https://doi.org/10.1074/jbc.M308929200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12939257"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12939257"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Devin T Rosenthal, Jie Zhang, Liwei Bao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RhoC impacts the metastatic potential and abundance of breast cancer stem cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0040979"}], "href": "https://doi.org/10.1371/journal.pone.0040979"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22911725"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22911725"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Mei Wu, Zhi-Fen Wu, Devin T Rosenthal, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Characterization of the roles of RHOC and RHOA GTPases in invasion, motility, and matrix adhesion in inflammatory and aggressive breast cancers."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/cncr.25181"}], "href": "https://doi.org/10.1002/cncr.25181"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20503409"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20503409"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Yasunori Shikada, Ichiro Yoshino, Tatsuro Okamoto, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Higher expression of RhoC is related to invasiveness in non-small cell lung carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Cancer Res (2003)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14614010"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14614010"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Wei Wang, Lian-Yue Yang, Zhi-Li Yang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression and significance of RhoC gene in hepatocellular carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "World J Gastroenterol (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3748/wjg.v9.i9.1950"}], "href": "https://doi.org/10.3748/wjg.v9.i9.1950"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12970882"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12970882"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Wei Wang, Fan Wu, Feng Fang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Inhibition of invasion and metastasis of hepatocellular carcinoma cells via targeting RhoC in vitro and in vivo."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Cancer Res (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/1078-0432.CCR-07-4820"}], "href": "https://doi.org/10.1158/1078-0432.CCR-07-4820"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18980974"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18980974"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Celina G Kleer, Theodoros N Teknos, Mozaffarul Islam, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RhoC GTPase expression as a potential marker of lymph node metastasis in squamous cell carcinomas of the head and neck."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Cancer Res (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/1078-0432.CCR-06-0376"}], "href": "https://doi.org/10.1158/1078-0432.CCR-06-0376"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16899593"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16899593"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Ahmad Faried, Leri S Faried, Nurhayat Usman, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Clinical and prognostic significance of RhoA and RhoC gene expression in esophageal squamous cell carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Ann Surg Oncol (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1245/s10434-007-9562-x"}], "href": "https://doi.org/10.1245/s10434-007-9562-x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17896152"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17896152"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Tomohiro Kondo, Kazuhiro Sentani, Naohide Oue, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression of RHOC is associated with metastasis of gastric carcinomas."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Pathobiology (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1159/000072958"}], "href": "https://doi.org/10.1159/000072958"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14555841"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14555841"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Na Liu, Guoyun Zhang, Feng Bi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RhoC is essential for the metastasis of gastric cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Mol Med (Berl) (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00109-007-0217-y"}], "href": "https://doi.org/10.1007/s00109-007-0217-y"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17549441"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17549441"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "Mozaffarul Islam, Smita Sharma, Theodoros N Teknos "}, {"type": "b", "children": [{"type": "t", "text": "RhoC regulates cancer stem cells in head and neck squamous cell carcinoma by overexpressing IL-6 and phosphorylation of STAT3."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0088527"}], "href": "https://doi.org/10.1371/journal.pone.0088527"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24533098"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24533098"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Mozaffarul Islam, Giant Lin, John C Brenner, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RhoC expression and head and neck cancer metastasis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cancer Res (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/1541-7786.MCR-08-0512"}], "href": "https://doi.org/10.1158/1541-7786.MCR-08-0512"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19861405"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19861405"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Wen-feng Gou, Yang Zhao, Hang Lu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The role of RhoC in epithelial-to-mesenchymal transition of ovarian carcinoma cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "BMC Cancer (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/1471-2407-14-477"}], "href": "https://doi.org/10.1186/1471-2407-14-477"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24986540"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24986540"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "T M Kitzing, Y Wang, O Pertz, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Formin-like 2 drives amoeboid invasive cell motility downstream of RhoC."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/onc.2009.515"}], "href": "https://doi.org/10.1038/onc.2009.515"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20101212"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20101212"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "William T Arthur, Shawn M Ellerbroek, Channing J Der, et al. "}, {"type": "b", "children": [{"type": "t", "text": "XPLN, a guanine nucleotide exchange factor for RhoA and RhoB, but not RhoC."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M207401200"}], "href": "https://doi.org/10.1074/jbc.M207401200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12221096"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12221096"}]}, {"type": "r", "ref": 28, "children": [{"type": "t", "text": "Dan-Dan Wu, Xi Chen, Kai-Xuan Sun, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Role of the lncRNA ABHD11-AS"}, {"type": "a", "children": [{"type": "t", "text": "sub"}], "href": "sub"}, {"type": "t", "text": "1"}, {"type": "a", "children": [{"type": "t", "text": "/sub"}], "href": "/sub"}, {"type": "t", "text": " in the tumorigenesis and progression of epithelial ovarian cancer through targeted regulation of RhoC."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cancer (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s12943-017-0709-5"}], "href": "https://doi.org/10.1186/s12943-017-0709-5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28818073"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28818073"}]}, {"type": "r", "ref": 29, "children": [{"type": "t", "text": "Koji Ueno, Hiroshi Hirata, Shahana Majid, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Tumor suppressor microRNA-493 decreases cell motility and migration ability in human bladder cancer cells by downregulating RhoC and FZD4."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cancer Ther (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/1535-7163.MCT-11-0592"}], "href": "https://doi.org/10.1158/1535-7163.MCT-11-0592"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22057916"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22057916"}]}, {"type": "r", "ref": 30, "children": [{"type": "t", "text": "Cheng-gong Liao, Ling-min Kong, Ping Zhou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "miR-10b is overexpressed in hepatocellular carcinoma and promotes cell proliferation, migration and invasion through RhoC, uPAR and MMPs."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Transl Med (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s12967-014-0234-x"}], "href": "https://doi.org/10.1186/s12967-014-0234-x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25236186"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25236186"}]}, {"type": "r", "ref": 31, "children": [{"type": "t", "text": "Jian Ming, Nan Liu, Yumei Gu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PRL-3 facilitates angiogenesis and metastasis by increasing ERK phosphorylation and up-regulating the levels and activities of Rho-A/C in lung cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Pathology (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/00313020802579268"}], "href": "https://doi.org/10.1080/00313020802579268"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19152186"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19152186"}]}, {"type": "r", "ref": 32, "children": [{"type": "t", "text": "Xi Chen, Shuo Chen, Yin-Ling Xiu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RhoC is a major target of microRNA-93-5P in epithelial ovarian carcinoma tumorigenesis and progression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cancer (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s12943-015-0304-6"}], "href": "https://doi.org/10.1186/s12943-015-0304-6"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25649143"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25649143"}]}, {"type": "r", "ref": 33, "children": [{"type": "t", "text": "Brant Hamel, Elizabeth Monaghan-Benson, Rafael J Rojas, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SmgGDS is a guanine nucleotide exchange factor that specifically activates RhoA and RhoC."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M110.191122"}], "href": "https://doi.org/10.1074/jbc.M110.191122"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21242305"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21242305"}]}, {"type": "r", "ref": 34, "children": [{"type": "t", "text": "Devin T Rosenthal, Harish Iyer, Silvia Escudero, et al. "}, {"type": "b", "children": [{"type": "t", "text": "p38γ promotes breast cancer cell motility and metastasis through regulation of RhoC GTPase, cytoskeletal architecture, and a novel leading edge behavior."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/0008-5472.CAN-11-1291"}], "href": "https://doi.org/10.1158/0008-5472.CAN-11-1291"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21862636"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21862636"}]}, {"type": "r", "ref": 35, "children": [{"type": "t", "text": "D Wu, M Asiedu, Q Wei "}, {"type": "b", "children": [{"type": "t", "text": "Myosin-interacting guanine exchange factor (MyoGEF) regulates the invasion activity of MDA-MB-231 breast cancer cells through activation of RhoA and RhoC."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/onc.2009.96"}], "href": "https://doi.org/10.1038/onc.2009.96"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19421144"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19421144"}]}, {"type": "r", "ref": 36, "children": [{"type": "t", "text": "Heather L Lehman, Steven J Van Laere, Cynthia M van Golen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulation of inflammatory breast cancer cell invasion through Akt1/PKBα phosphorylation of RhoC GTPase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cancer Res (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/1541-7786.MCR-12-0173"}], "href": "https://doi.org/10.1158/1541-7786.MCR-12-0173"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22896661"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22896661"}]}, {"type": "r", "ref": 37, "children": [{"type": "t", "text": "S Srivastava, B Ramdass, S Nagarajan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Notch1 regulates the functional contribution of RhoC to cervical carcinoma progression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Br J Cancer (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.bjc.6605451"}], "href": "https://doi.org/10.1038/sj.bjc.6605451"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19953094"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19953094"}]}, {"type": "r", "ref": 38, "children": [{"type": "t", "text": "Melpomeni Tseliou, Ahmed Al-Qahtani, Saud Alarifi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Role of RhoA, RhoB and RhoC GTPases in Cell Morphology, Proliferation and Migration in Human Cytomegalovirus (HCMV) Infected Glioblastoma Cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Physiol Biochem (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1159/000438612"}], "href": "https://doi.org/10.1159/000438612"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26741994"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26741994"}]}, {"type": "r", "ref": 39, "children": [{"type": "t", "text": "Hooi Ching Lim, John R Couchman "}, {"type": "b", "children": [{"type": "t", "text": "Syndecan-2 regulation of morphology in breast carcinoma cells is dependent on RhoGTPases."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbagen.2014.01.018"}], "href": "https://doi.org/10.1016/j.bbagen.2014.01.018"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24447566"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24447566"}]}, {"type": "r", "ref": 40, "children": [{"type": "t", "text": "Daniel R Croft, Diane Crighton, Michael S Samuel, et al. "}, {"type": "b", "children": [{"type": "t", "text": "p53-mediated transcriptional regulation and activation of the actin cytoskeleton regulatory RhoC to LIMK2 signaling pathway promotes cell survival."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Res (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/cr.2010.154"}], "href": "https://doi.org/10.1038/cr.2010.154"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21079653"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21079653"}]}, {"type": "r", "ref": 41, "children": [{"type": "t", "text": "Haixia Yang, Jiupeng Zhou, Jianqiang Mi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "HOXD10 acts as a tumor-suppressive factor via inhibition of the RHOC/AKT/MAPK pathway in human cholangiocellular carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncol Rep (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/or.2015.4194"}], "href": "https://doi.org/10.3892/or.2015.4194"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26260613"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26260613"}]}, {"type": "r", "ref": 42, "children": [{"type": "t", "text": "Pavana Thomas, Annapurna Pranatharthi, Cecil Ross, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RhoC: a fascinating journey from a cytoskeletal organizer to a Cancer stem cell therapeutic target."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Exp Clin Cancer Res (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s13046-019-1327-4"}], "href": "https://doi.org/10.1186/s13046-019-1327-4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31340863"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31340863"}]}]}]}