國家衛生研究院 NHRI:Item 3990099045/13522

NHRI > National Institute of Environmental Health Sciences > Tsui-Chun Tsou > Periodical Articles > Item 3990099045/13522

Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/13522

Title:	FOXM1 is required for small cell lung cancer tumorigenesis and associated with poor clinical prognosis
Authors:	Liang, SK;Hsu, CC;Song, HL;Huang, YC;Kuo, CW;Yao, X;Li, CC;Yang, HC;Hung, YL;Chao, SY;Wu, SC;Tsai, FR;Chen, JK;Liao, WN;Cheng, SC;Tsou, TC;Wang, IC
Contributors:	National Institute of Environmental Health Sciences;Institute of Biomedical Engineering and Nanomedicine
Abstract:	Small cell lung cancer (SCLC) continues to cause poor clinical outcomes due to limited advances in sustained treatments for rapid cancer cell proliferation and progression. The transcriptional factor Forkhead Box M1 (FOXM1) regulates cell proliferation, tumor initiation, and progression in multiple cancer types. However, its biological function and clinical significance in SCLC remain unestablished. Analysis of the Cancer Cell Line Encyclopedia and SCLC datasets in the present study disclosed significant upregulation of FOXM1 mRNA in SCLC cell lines and tissues. Gene set enrichment analysis (GSEA) revealed that FOXM1 is positively correlated with pathways regulating cell proliferation and DNA damage repair, as evident from sensitization of FOXM1-depleted SCLC cells to chemotherapy. Furthermore, Foxm1 knockout inhibited SCLC formation in the Rb1(fl/fl)Trp53(fl/fl)Myc(LSL/LSL) (RPM) mouse model associated with increased levels of neuroendocrine markers, Ascl1 and Cgrp, and decrease in Yap1. Consistently, FOXM1 depletion in NCI-H1688 SCLC cells reduced migration and enhanced apoptosis and sensitivity to cisplatin and etoposide. SCLC with high FOXM1 expression (N = 30, 57.7%) was significantly correlated with advanced clinical stage, extrathoracic metastases, and decrease in overall survival (OS), compared with the low-FOXM1 group (7.90 vs. 12.46 months). Moreover, the high-FOXM1 group showed shorter progression-free survival after standard chemotherapy, compared with the low-FOXM1 group (3.90 vs. 8.69 months). Our collective findings support the utility of FOXM1 as a prognostic biomarker and potential molecular target for SCLC.
Date:	2021-07
Relation:	Oncogene. 2021 Jul;40(30):4847-4858.
Link to:	http://dx.doi.org/10.1038/s41388-021-01895-2
JIF/Ranking 2023:	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0950-9232&DestApp=IC2JCR
Cited Times(WOS):	https://www.webofscience.com/wos/woscc/full-record/WOS:000664006700004
Cited Times(Scopus):	https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85108295539
Appears in Collections:	[Tsui-Chun Tsou] Periodical Articles [Jen-Kun Chen] Periodical Articles

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