Oncotarget

Research Papers:

FGF4 induces epithelial-mesenchymal transition by inducing store-operated calcium entry in lung adenocarcinoma

Lisha Qi, Wangzhao Song, Lingmei Li, Lu Cao, Yue Yu, Chunmin Song, Yalei Wang, Fei Zhang, Yang Li, Bin Zhang _ and Wenfeng Cao

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Oncotarget. 2016; 7:74015-74030. https://doi.org/10.18632/oncotarget.12187

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Abstract

Lisha Qi1,5,6, Wangzhao Song1,4,5,6, Lingmei Li1,5,6, Lu Cao1,4,5,6, Yue Yu2,5,6, Chunmin Song8, Yalei Wang1,5,6, Fei Zhang5,6,7, Yang Li3,4,5,6, Bin Zhang2,5,6, Wenfeng Cao1,5,6

1Department of Pathology, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China

2Department of Breast Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China

3Department of Pancreatic Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China

4Tianjin Medical University, Tianjin 300070, China

5The Key Laboratory of Tianjin Cancer Prevention and Treatment, Tianjin 300060, China

6National Clinical Research Center for Cancer, Tianjin 300060, China

7Research Center of Basic Medical Sciences, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China

8Department of Family Planning, Maternity & Child Care Center of Luoyang, Luoyang 471000, China

Correspondence to:

Bin Zhang, email: eeflying@163.com

Wenfeng Cao, email: caowenfeng@tjmuch.com

Keywords: FGF4, epithelial-mesenchymal transition, store-operated calcium entry, Orai1, FGF7

Received: February 04, 2016     Accepted: August 23, 2016     Published: September 22, 2016

ABSTRACT

Several fibroblast growth factor (FGF) isoforms act to stimulate epithelial-mesenchymal transition (EMT) during cancer progression. FGF4 and FGF7 are two ligands of FGF receptor 2 (FGFR2). Using two lung adenocarcinoma (ADC) cell lines, A549 and H1299, we showed that FGF4, but not FGF7, altered cell morphology, promoted EMT-associated protein expression, and enhanced cell proliferation, migration/invasion and colony initiation. In addition, FGF4 increased store-operated calcium entry (SOCE) and expression of the calcium signal-associated protein Orai1. The SOCE inhibitor 2,5-di-tert-butylhydroquinone (BHQ) or Orai1 knockdown reversed all of the EMT-promoting effects of FGF4. BHQ also inhibited FGF4-induced EMT in a mouse xenograft model. Finally, 60 human lung ADC samples and 21 sets of matched specimens (primary and metastatic foci in lymph nodes from one patient) were used to confirm the clinicopathologic significance of FGF4 and its correlation with E-cadherin, Vimentin and Orai1 expression. Our study thus shows that FGF4 induces EMT by elevating SOCE in lung ADC.


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