Abstract
Forkhead box Q1 (FoxQ1) is a member of the forkhead transcription factor family. High expression of FoxQ1 has been associated with several cancers including non-small cell lung cancer (NSCLC), but its role in the development of NSCLC is not clear. In this study, we investigated the effect of FoxQ1 up-regulated and down-regulated in vitro and in vivo, and the role of FoxQ1 in regulating epithelial-mesenchymal transition (EMT) in NSCLC, providing evidence that FoxQ1 could be a potential therapeutic target in NSCLC. NSCLC cells with silenced FoxQ1 had decreased cell proliferation, migration and invasion in cell culture and delayed growth of xenograft tumors in mice compared with corresponding control cells. The NSCLC cells downregulated for FoxQ1 induced the expression of apoptosis-associated proteins and reduction of anti-apoptotic protein expression. Downregulation of FoxQ1 promoted the expression of epithelial markers and decreased several mesenchymal markers in vitro and in vivo. In addition, FoxQ1 was associated with resistance to conventional chemotherapeutic agents. In contrast, FoxQ1 overexpressed elicited converse effects on these phenotypes in vitro and in vivo. Our findings define a key role for FoxQ1 in regulating EMT and increasing chemosensitivity in NSCLC.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Apoptosis / drug effects
-
Apoptosis / genetics
-
Apoptosis / physiology
-
Carcinoma, Non-Small-Cell Lung / drug therapy*
-
Carcinoma, Non-Small-Cell Lung / genetics
-
Carcinoma, Non-Small-Cell Lung / metabolism*
-
Carcinoma, Non-Small-Cell Lung / pathology
-
Cell Line, Tumor
-
Cell Movement / physiology
-
Cell Proliferation / physiology
-
Cisplatin / pharmacology
-
Deoxycytidine / analogs & derivatives
-
Deoxycytidine / pharmacology
-
Docetaxel
-
Down-Regulation
-
Drug Resistance, Neoplasm
-
Epithelial-Mesenchymal Transition / genetics
-
Forkhead Transcription Factors / biosynthesis
-
Forkhead Transcription Factors / genetics
-
Forkhead Transcription Factors / metabolism*
-
Gemcitabine
-
Gene Expression Regulation, Neoplastic
-
Gene Silencing
-
Glutamates / pharmacology
-
Guanine / analogs & derivatives
-
Guanine / pharmacology
-
Heterografts
-
Humans
-
Lung Neoplasms / drug therapy*
-
Lung Neoplasms / genetics
-
Lung Neoplasms / metabolism*
-
Lung Neoplasms / pathology
-
Mice
-
Mice, Inbred BALB C
-
Mice, Nude
-
Neoplasm Invasiveness
-
Pemetrexed
-
RNA, Messenger / genetics
-
RNA, Messenger / metabolism
-
Taxoids / pharmacology
Substances
-
FOXQ1 protein, human
-
Forkhead Transcription Factors
-
Glutamates
-
RNA, Messenger
-
Taxoids
-
Pemetrexed
-
Deoxycytidine
-
Docetaxel
-
Guanine
-
Cisplatin
-
Gemcitabine