{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSRCIN1, also known as p140Cap, is an adaptor protein that plays a crucial role in dampening Src kinase activity and its downstream pathways, thereby regulating cell proliferation, adhesion, and migration. Experimental studies have shown that SRCIN1/p140Cap binds Src and activates its negative regulator, C‐terminal Src kinase (Csk), which leads to the inhibition of signaling cascades including those mediated by EGFR, FAK, ERK, and Ras. In several cancers – for example, in lung and gastric carcinomas – decreased SRCIN1 expression (often resulting from microRNA targeting) is associated with enhanced Src activity and increased cell proliferation and invasion. These findings underscore its tumor‐suppressive function in diverse cellular contexts."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn various malignancies, post‐transcriptional regulation by non‐coding RNAs emerges as a common mechanism to alter SRCIN1 levels. MicroRNAs such as miR‑20a‑5p, miR‑17‑5p, miR‑150, miR‑211, miR‑346, miR‑510, and miR‑208a have been demonstrated to directly target the 3\u2032‐UTR of SRCIN1 transcripts in contexts including osteosarcoma, non–small cell lung cancer, pancreatic cancer, and breast cancer. In these studies, diminished SRCIN1 expression—whether via microRNA overexpression or through alterations in associated circular RNAs—leads to the release of Src activity, triggering enhanced downstream signaling (for example, via FAK, ERK, STAT3 and even Wnt/\u03b2-catenin) that promotes proliferation, migration, invasion, metastasis, and even drug resistance. Moreover, in some settings, SRCIN1 reduction facilitates osteoclast differentiation and bone metastasis or contributes to aberrant cell cycle progression."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "10", "end_ref": "18"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nClinically, alterations in SRCIN1 expression or epigenetic regulation have significant prognostic and therapeutic implications. In breast cancer, neuroblastoma, colorectal cancer, and others, reduced SRCIN1 levels—whether by microRNA-mediated suppression, altered sponging by long non-coding or circular RNAs, or aberrant hypermethylation—correlate with aggressive tumor behavior and poorer survival outcomes. These studies indicate that SRCIN1 not only serves as an essential mediator of oncogenic signaling but may also function as a predictive biomarker and potential therapeutic target. Recent reviews and translational investigations further highlight the multifaceted role of the SRCIN1/p140Cap axis in controlling both tumor cell–intrinsic properties and the tumor microenvironment."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "19", "end_ref": "23"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Paola Di Stefano, Laura Damiano, Sara Cabodi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "p140Cap protein suppresses tumour cell properties, regulating Csk and Src kinase activity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO J (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.emboj.7601724"}], "href": "https://doi.org/10.1038/sj.emboj.7601724"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17525734"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17525734"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "S Kennedy, M Clynes, P Doolan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SNIP/p140Cap mRNA expression is an unfavourable prognostic factor in breast cancer and is not expressed in normal breast tissue."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Br J Cancer (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.bjc.6604365"}], "href": "https://doi.org/10.1038/sj.bjc.6604365"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18475297"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18475297"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "L Damiano, P Di Stefano, M P Camacho Leal, et al. "}, {"type": "b", "children": [{"type": "t", "text": "p140Cap dual regulation of E-cadherin/EGFR cross-talk and Ras signalling in tumour cell scatter and proliferation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/onc.2010.128"}], "href": "https://doi.org/10.1038/onc.2010.128"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20453886"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20453886"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Daniele Repetto, Simona Aramu, Elisabetta Boeri Erba, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mapping of p140Cap phosphorylation sites: the EPLYA and EGLYA motifs have a key role in tyrosine phosphorylation and Csk binding, and are substrates of the Abl kinase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0054931"}], "href": "https://doi.org/10.1371/journal.pone.0054931"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23383002"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23383002"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Minghui Cao, Dongxia Hou, Hongwei Liang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "miR-150 promotes the proliferation and migration of lung cancer cells by targeting SRC kinase signalling inhibitor 1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Cancer (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ejca.2013.12.024"}], "href": "https://doi.org/10.1016/j.ejca.2013.12.024"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24456795"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24456795"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Xinyun Xu, Weijun Wang, Ning Su, et al. "}, {"type": "b", "children": [{"type": "t", "text": "miR-374a promotes cell proliferation, migration and invasion by targeting SRCIN1 in gastric cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FEBS Lett (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.febslet.2014.12.027"}], "href": "https://doi.org/10.1016/j.febslet.2014.12.027"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25554419"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25554419"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Yanrui Yang, Mengping Wei, Ying Xiong, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Endophilin A1 regulates dendritic spine morphogenesis and stability through interaction with p140Cap."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Res (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/cr.2015.31"}], "href": "https://doi.org/10.1038/cr.2015.31"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25771685"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25771685"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Leiguang Ye, Hui Wang, Baogang Liu "}, {"type": "b", "children": [{"type": "t", "text": "miR-211 promotes non-small cell lung cancer proliferation by targeting SRCIN1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Tumour Biol (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s13277-015-3835-y"}], "href": "https://doi.org/10.1007/s13277-015-3835-y"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26277787"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26277787"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Fan Yang, Long-Ji Luo, Lei Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MiR-346 promotes the biological function of breast cancer cells by targeting SRCIN1 and reduces chemosensitivity to docetaxel."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gene (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.gene.2016.11.037"}], "href": "https://doi.org/10.1016/j.gene.2016.11.037"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27913185"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27913185"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Silvia Grasso, Jennifer Chapelle, Vincenzo Salemme, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The scaffold protein p140Cap limits ERBB2-mediated breast cancer progression interfering with Rac GTPase-controlled circuitries."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncomms14797"}], "href": "https://doi.org/10.1038/ncomms14797"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28300085"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28300085"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Mengnan Zhang, Feng Ma, Ruyi Xie, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Overexpression of Srcin1 contributes to the growth and metastasis of colorectal cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Oncol (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/ijo.2017.3952"}], "href": "https://doi.org/10.3892/ijo.2017.3952"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28393242"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28393242"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Min-Yin Li, Wan-Ying Miao, Qiu-Zi Wu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A Critical Role of Presynaptic Cadherin/Catenin/p140Cap Complexes in Stabilizing Spines and Functional Synapses in the Neocortex."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neuron (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.neuron.2017.05.022"}], "href": "https://doi.org/10.1016/j.neuron.2017.05.022"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28641114"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28641114"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Xuefeng Zhao, Yan Xu, Xiaoya Sun, et al. "}, {"type": "b", "children": [{"type": "t", "text": "miR-17-5p promotes proliferation and epithelial-mesenchymal transition in human osteosarcoma cells by targeting SRC kinase signaling inhibitor 1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biochem (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jcb.27832"}], "href": "https://doi.org/10.1002/jcb.27832"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30302813"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30302813"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Wenbin Wang, Xingyang Zhu, Xiaolong Du, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MiR-150 promotes angiogensis and proliferation of endothelial progenitor cells in deep venous thrombosis by targeting SRCIN1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Microvasc Res (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.mvr.2018.10.003"}], "href": "https://doi.org/10.1016/j.mvr.2018.10.003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30315850"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30315850"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Liangliang Ma, Zhijiang Shao, Yunbo Zhao "}, {"type": "b", "children": [{"type": "t", "text": "MicroRNA-374a promotes pancreatic cancer cell proliferation and epithelial to mesenchymal transition by targeting SRCIN1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Pathol Res Pract (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.prp.2019.03.011"}], "href": "https://doi.org/10.1016/j.prp.2019.03.011"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30890278"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30890278"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Wei Wu, Linyan He, Yan Huang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MicroRNA-510 Plays Oncogenic Roles in Non-Small Cell Lung Cancer by Directly Targeting SRC Kinase Signaling Inhibitor 1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncol Res (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3727/096504018X15451308507747"}], "href": "https://doi.org/10.3727/096504018X15451308507747"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30982489"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30982489"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Ling Guo, Ye Zhu, Liandi Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Breast cancer cell-derived exosomal miR-20a-5p promotes the proliferation and differentiation of osteoclasts by targeting SRCIN1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Med (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/cam4.2454"}], "href": "https://doi.org/10.1002/cam4.2454"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31385464"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31385464"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Li Liu, Wuzhang Wang, Song Gao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MicroRNA‑208a directly targets Src kinase signaling inhibitor 1 to facilitate cell proliferation and invasion in non‑small cell lung cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Med Rep (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/mmr.2019.10542"}], "href": "https://doi.org/10.3892/mmr.2019.10542"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31432113"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31432113"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Feng Cao, Zhiguo Wang, Yong Feng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "lncRNA TPTEP1 competitively sponges miR‑328‑5p to inhibit the proliferation of non‑small cell lung cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncol Rep (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/or.2020.7522"}], "href": "https://doi.org/10.3892/or.2020.7522"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32323798"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32323798"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Weijun Hong, Suyun Yu, Yaqing Zhuang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SRCIN1 Regulated by circCCDC66/miR-211 Is Upregulated and Promotes Cell Proliferation in Non-Small-Cell Lung Cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biomed Res Int (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1155/2020/5307641"}], "href": "https://doi.org/10.1155/2020/5307641"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32964035"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32964035"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Vincenzo Salemme, Costanza Angelini, Jennifer Chapelle, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The p140Cap adaptor protein as a molecular hub to block cancer aggressiveness."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Mol Life Sci (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00018-020-03666-w"}], "href": "https://doi.org/10.1007/s00018-020-03666-w"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33079227"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33079227"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Vincenzo Salemme, Mauro Vedelago, Alessandro Sarcinella, et al. "}, {"type": "b", "children": [{"type": "t", "text": "p140Cap inhibits β-Catenin in the breast cancer stem cell compartment instructing a protective anti-tumor immune response."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-023-37824-y"}], "href": "https://doi.org/10.1038/s41467-023-37824-y"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37169737"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37169737"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "Hsieh-Tsung Shen, Chin-Sheng Hung, Clilia Davis, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hypermethylation of the Gene Body in "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "SRCIN1"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": " Is Involved in Breast Cancer Cell Proliferation and Is a Potential Blood-Based Biomarker for Early Detection and a Poor Prognosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biomolecules (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/biom14050571"}], "href": "https://doi.org/10.3390/biom14050571"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38785978"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38785978"}]}]}]}