{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Anterior gradient 2 (AGR2) is a multifunctional protein whose activities span from the endoplasmic reticulum (ER) to the extracellular milieu, contributing significantly to both normal epithelial physiology and tumor progression. In the ER, AGR2 functions as a protein disulfide isomerase that contacts nascent secretory proteins to ensure proper folding and maturation. Its activity is critical for the production and processing of large, cysteine‐rich mucins such as MUC2 in intestinal goblet cells, thereby supporting mucosal barrier integrity and preventing inflammation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": " In addition, AGR2 expression is tightly linked to the differentiation programme of secretory epithelial cells in both the gastrointestinal and pulmonary tracts, often being induced by transcriptional regulators such as SPDEF and FOXA factors to promote goblet cell differentiation and mucus production."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its homeostatic roles, AGR2 is frequently overexpressed in a wide range of adenocarcinomas—including those of the pancreas, prostate, breast, esophagus, lung, and ovary—where it often becomes secreted and exerts extracellular functions. In cancer, AGR2 promotes cell transformation, migration, invasion, and metastasis by modulating protein folding quality control and by activating growth‐promoting pathways (for example, by inducing amphiregulin via YAP1 activation)."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "8"}]}, {"type": "t", "text": " Moreover, AGR2’s expression is regulated by hormonal cues (as seen in prostate and breast cancers where it is androgen‐ and estrogen‐responsive, respectively), and its levels can correlate with both favorable differentiation markers and, paradoxically, with enhanced metastatic potential and poor survival outcomes."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "12"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the context of inflammatory and stress‐related conditions, AGR2 not only helps maintain ER homeostasis and protect against ER stress but also appears to be modulated by environmental parameters such as hypoxia and nutrient deprivation, suggesting its induction under adverse conditions can foster a pro‐metastatic phenotype."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": " Furthermore, changes in its gene regulation, as in inflammatory bowel disease, underscore a role in maintaining epithelial integrity and proper secretory function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": " Finally, secreted AGR2 (eAGR2) has been shown to interact with extracellular matrix components, thereby altering cell–matrix interactions and promoting invasive properties—a function that is independent of its classical ER role."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "15"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, AGR2 is a critical regulator of both normal epithelial differentiation and mucin production as well as a potent mediator of neoplastic transformation and metastasis. Its multifaceted roles—ranging from facilitating proper protein folding in the ER to remodeling the tumor microenvironment extracellularly—render AGR2 a compelling therapeutic target and prognostic marker across diverse diseases."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}, {"type": "fg_f", "ref": "6"}, {"type": "fg_f", "ref": "16"}, {"type": "fg_f", "ref": "4"}, {"type": "fg_f", "ref": "7"}, {"type": "fg_fs", "start_ref": "17", "end_ref": "19"}, {"type": "fg_f", "ref": "9"}, {"type": "fg_f", "ref": "20"}, {"type": "fg_f", "ref": "14"}, {"type": "fg_f", "ref": "21"}, {"type": "fg_f", "ref": "10"}, {"type": "fg_f", "ref": "22"}, {"type": "fg_f", "ref": "8"}, {"type": "fg_f", "ref": "12"}, {"type": "fg_fs", "start_ref": "23", "end_ref": "25"}, {"type": "fg_f", "ref": "11"}, {"type": "fg_f", "ref": "26"}, {"type": "fg_f", "ref": "5"}, {"type": "fg_f", "ref": "13"}, {"type": "fg_f", "ref": "15"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Gang Chen, Thomas R Korfhagen, Yan Xu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SPDEF is required for mouse pulmonary goblet cell differentiation and regulates a network of genes associated with mucus production."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI39731"}], "href": "https://doi.org/10.1172/JCI39731"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19759516"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19759516"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Sung-Woo Park, Guohua Zhen, Catherine Verhaeghe, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The protein disulfide isomerase AGR2 is essential for production of intestinal mucus."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0808722106"}], "href": "https://doi.org/10.1073/pnas.0808722106"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19359471"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19359471"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Fang Zhao, Robert Edwards, Diana Dizon, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Disruption of Paneth and goblet cell homeostasis and increased endoplasmic reticulum stress in Agr2-/- mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Dev Biol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ydbio.2009.12.008"}], "href": "https://doi.org/10.1016/j.ydbio.2009.12.008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20025862"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20025862"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Taeko K Noah, Avedis Kazanjian, Jeffrey Whitsett, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SAM pointed domain ETS factor (SPDEF) regulates terminal differentiation and maturation of intestinal goblet cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Exp Cell Res (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.yexcr.2009.09.020"}], "href": "https://doi.org/10.1016/j.yexcr.2009.09.020"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19786015"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19786015"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Hongmei Yu, Qi Li, Victor P Kolosov, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Interleukin-13 induces mucin 5AC production involving STAT6/SPDEF in human airway epithelial cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Commun Adhes (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3109/15419061.2010.551682"}], "href": "https://doi.org/10.3109/15419061.2010.551682"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21275604"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21275604"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Zheng Wang, Ying Hao, Anson W Lowe "}, {"type": "b", "children": [{"type": "t", "text": "The adenocarcinoma-associated antigen, AGR2, promotes tumor growth, cell migration, and cellular transformation."}]}, {"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-07-2930"}], "href": "https://doi.org/10.1158/0008-5472.CAN-07-2930"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18199544"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18199544"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Vijaya Ramachandran, Thiruvengadam Arumugam, Huamin Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Anterior gradient 2 is expressed and secreted during the development of pancreatic cancer and promotes cancer cell survival."}]}, {"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-08-1320"}], "href": "https://doi.org/10.1158/0008-5472.CAN-08-1320"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18829536"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18829536"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Aiwen Dong, Aparna Gupta, Reetesh K Pai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The human adenocarcinoma-associated gene, AGR2, induces expression of amphiregulin through Hippo pathway co-activator YAP1 activation."}]}, {"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.M110.215707"}], "href": "https://doi.org/10.1074/jbc.M110.215707"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21454516"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21454516"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Jin-San Zhang, Aiyu Gong, John C Cheville, et al. "}, {"type": "b", "children": [{"type": "t", "text": "AGR2, an androgen-inducible secretory protein overexpressed in prostate cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Chromosomes Cancer (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/gcc.20188"}], "href": "https://doi.org/10.1002/gcc.20188"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15834940"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15834940"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Florian Rudolf Fritzsche, Edgar Dahl, Stefan Pahl, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Prognostic relevance of AGR2 expression in breast cancer."}]}, {"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-05-2057"}], "href": "https://doi.org/10.1158/1078-0432.CCR-05-2057"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16551856"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16551856"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Dong L Barraclough, Angela Platt-Higgins, Suzete de Silva Rudland, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The metastasis-associated anterior gradient 2 protein is correlated with poor survival of breast cancer patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Pathol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2353/ajpath.2009.090246"}], "href": "https://doi.org/10.2353/ajpath.2009.090246"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19834055"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19834055"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Huajie Bu, Stefanie Bormann, Georg Schäfer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The anterior gradient 2 (AGR2) gene is overexpressed in prostate cancer and may be useful as a urine sediment marker for prostate cancer detection."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Prostate (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/pros.21273"}], "href": "https://doi.org/10.1002/pros.21273"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20945500"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20945500"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Daniel R Zweitzig, Denis A Smirnov, Mark C Connelly, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Physiological stress induces the metastasis marker AGR2 in breast cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biochem (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s11010-007-9562-y"}], "href": "https://doi.org/10.1007/s11010-007-9562-y"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17694278"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17694278"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "W Zheng, P Rosenstiel, K Huse, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Evaluation of AGR2 and AGR3 as candidate genes for inflammatory bowel disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Immun (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.gene.6364263"}], "href": "https://doi.org/10.1038/sj.gene.6364263"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16222343"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16222343"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Delphine Fessart, Charlotte Domblides, Tony Avril, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Secretion of protein disulphide isomerase AGR2 confers tumorigenic properties."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Elife (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.7554/eLife.13887"}], "href": "https://doi.org/10.7554/eLife.13887"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27240165"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27240165"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "G C Fletcher, S Patel, K Tyson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "hAG-2 and hAG-3, human homologues of genes involved in differentiation, are associated with oestrogen receptor-positive breast tumours and interact with metastasis gene C4.4a and dystroglycan."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Br J Cancer (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.bjc.6600740"}], "href": "https://doi.org/10.1038/sj.bjc.6600740"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12592373"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12592373"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "David H Tompkins, Valérie Besnard, Alexander W Lange, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Sox2 is required for maintenance and differentiation of bronchiolar Clara, ciliated, and goblet cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0008248"}], "href": "https://doi.org/10.1371/journal.pone.0008248"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20011520"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20011520"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "M B Martino, L Jones, B Brighton, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The ER stress transducer IRE1β is required for airway epithelial mucin production."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mucosal Immunol (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/mi.2012.105"}], "href": "https://doi.org/10.1038/mi.2012.105"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23168839"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23168839"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Laurent Dumartin, Hannah J Whiteman, Mark E Weeks, et al. "}, {"type": "b", "children": [{"type": "t", "text": "AGR2 is a novel surface antigen that promotes the dissemination of pancreatic cancer cells through regulation of cathepsins B and D."}]}, {"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-11-1367"}], "href": "https://doi.org/10.1158/0008-5472.CAN-11-1367"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21948970"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21948970"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "E Chevet, D Fessart, F Delom, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Emerging roles for the pro-oncogenic anterior gradient-2 in cancer development."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/onc.2012.346"}], "href": "https://doi.org/10.1038/onc.2012.346"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22945652"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22945652"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Arisa Higa, Audrey Mulot, Frédéric Delom, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Role of pro-oncogenic protein disulfide isomerase (PDI) family member anterior gradient 2 (AGR2) in the control of endoplasmic reticulum homeostasis."}]}, {"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.M111.275529"}], "href": "https://doi.org/10.1074/jbc.M111.275529"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22025610"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22025610"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Emmanuel Di Valentin, Céline Crahay, Nancy Garbacki, et al. "}, {"type": "b", "children": [{"type": "t", "text": "New asthma biomarkers: lessons from murine models of acute and chronic asthma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Lung Cell Mol Physiol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajplung.90367.2008"}], "href": "https://doi.org/10.1152/ajplung.90367.2008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19028979"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19028979"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "Kathryn E Vanderlaag, Susan Hudak, Laura Bald, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Anterior gradient-2 plays a critical role in breast cancer cell growth and survival by modulating cyclin D1, estrogen receptor-alpha and survivin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Breast Cancer Res (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/bcr2586"}], "href": "https://doi.org/10.1186/bcr2586"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20525379"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20525379"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Kyoungsook Park, Yong Jin Chung, Hyekyung So, et al. "}, {"type": "b", "children": [{"type": "t", "text": "AGR2, a mucinous ovarian cancer marker, promotes cell proliferation and migration."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Exp Mol Med (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3858/emm.2011.43.2.011"}], "href": "https://doi.org/10.3858/emm.2011.43.2.011"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21200134"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21200134"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "David H Wang, Anjana Tiwari, Monica E Kim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hedgehog signaling regulates FOXA2 in esophageal embryogenesis and Barrett's metaplasia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI66603"}], "href": "https://doi.org/10.1172/JCI66603"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25083987"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25083987"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "L Dumartin, W Alrawashdeh, S M Trabulo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ER stress protein AGR2 precedes and is involved in the regulation of pancreatic cancer initiation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/onc.2016.459"}], "href": "https://doi.org/10.1038/onc.2016.459"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27941872"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27941872"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "Y Zhang, S S Forootan, D Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Increased expression of anterior gradient-2 is significantly associated with poor survival of prostate cancer patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Prostate Cancer Prostatic Dis (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.pcan.4500960"}], "href": "https://doi.org/10.1038/sj.pcan.4500960"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17457305"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17457305"}]}]}]}