Open AccessGrainyhead‐like 2 ( GRHL 2) regulates epithelial plasticity in pancreatic cancer progression
Author(s) -
Nishino Hitoe,
Takano Shigetsugu,
Yoshitomi Hideyuki,
Suzuki Kensuke,
Kagawa Shingo,
Shimazaki Reiri,
Shimizu Hiroaki,
Furukawa Katsunori,
Miyazaki Masaru,
Ohtsuka Masayuki
Publication year - 2017
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.1212
Subject(s) - gene knockdown , metastasis , epithelial–mesenchymal transition , cancer research , biology , pancreatic cancer , anoikis , mesenchymal stem cell , flow cytometry , ectopic expression , cancer , pathology , cell culture , microbiology and biotechnology , immunology , medicine , genetics
The epithelial‐mesenchymal transition ( EMT ) and mesenchymal‐epithelial transition ( MET ) contribute to cancer metastasis of pancreatic ductal adenocarcinoma ( PDAC ). We explored the role of grainyhead‐like 2 ( GRHL 2), a suppressor of EMT , in the progression of PDAC . Expressions of GRHL 2 were assessed using surgically resected PDAC tissues by immunohistochemistry analysis, and in vitro using human and mouse PDAC cells. Effects on epithelial plasticity and stemness of GRHL 2 were examined in vitro using liver metastatic PDAC cells ( CFPAC ‐1) with GRHL 2 knockdown by specific si RNA s. GRHL 2 has a significantly positive correlation with E‐cadherin and CD 133 in 155 resected human primary PDAC tissues. GRHL 2 is highly expressed in liver metastatic cells than in primary invasive cells of both human and mouse PDAC , accompanied by a positive correlation with E‐cadherin expression. GRHL 2 knockdown CFPAC ‐1 cells demonstrated morphological changes into mesenchymal appearances and reduced proliferation through EMT . Notably, knockdown studies followed by flow cytometry analysis for a subpopulation of CD 133+ showed that GRHL 2 facilitates CFPAC ‐1 cells to maintain stem‐like characters including self‐renewal capacity and anoikis resistance. GRHL 2 regulates epithelial plasticity along with stemness in PDAC , both of which are crucial for metastasis, implicating the possibility of GRHL 2 as a therapeutic target for PDAC liver metastasis.