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Role of SET oncoprotein in epithelial‐mesenchymal transition and pancreatic cancer progression (784.3)
Author(s) -
Hung Sau Wai,
Lee Haesung,
Gilbert Caitlin,
Hoang Toan,
Naidu Kineta,
Govindarajan Rajgopal
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.784.3
Subject(s) - epithelial–mesenchymal transition , cancer research , pancreatic cancer , metastasis , cadherin , gene silencing , biology , slug , cell migration , tumor progression , signal transduction , rac1 , cancer , cell , medicine , microbiology and biotechnology , gene , biochemistry , genetics
One of the key reasons for why pancreatic cancer has such a poor prognosis is that >80% of diagnoses occur when metastasis has already presented. At the cellular level, activation of the epithelial‐mesenchymal transition (EMT) is significant because it allows for the dissemination of primary tumor cells to distant sites. In this study, we sought to determine the role of a novel oncoprotein, SET, in EMT and pancreatic cancer cell progression. We found that silencing SET reverted EMT by inducing a cuboidal, epithelial morphology and reducing colony formation, cellular proliferation, migration, and invasion. Consistently, SET overexpression was detected in a subset of pancreatic tumors, especially poorly‐differentiated pancreatic ductal adenocarcinomas. Higher levels of SET protein expression were also identified in all pancreatic cancer cell lines compared with normal human pancreatic ductal epithelial cells. SET‐mediated EMT was determined to be a result of cadherin switching during which the SPARC/Slug and Rac1/JNK/c‐Jun/AP‐1 signaling pathways inhibit epithelial E‐cadherin and promote mesenchymal N‐cadherin, respectively. In brief, we elucidated a novel role for the SET protein in inducing EMT through cadherin switching and revealed the molecular pathways involved. These findings have implications for the design and targeting of pathways necessary for intervening pancreatic tumor progression. Grant Funding Source : Supported by NIH 1021RR571367 and 1021RR571381.