FOXC2 promotes colorectal cancer proliferation through inhibition of FOXO3a and activation of MAPK and AKT signaling pathways

Yan-Mei Cui; Dan Jiang; Shi-Hong Zhang; Ping Wu; Ya-Ping Ye; Cui-Min Chen; Na Tang; Li Liang; Ting-Ting Li; Lu Qi; Shu-Yang Wang; Hong-Li Jiao; Jie Lin; Yan-Qing Ding; Wen-Ting Liao

doi:10.1016/j.canlet.2014.07.008

FOXC2 promotes colorectal cancer proliferation through inhibition of FOXO3a and activation of MAPK and AKT signaling pathways

Cancer Lett. 2014 Oct 10;353(1):87-94. doi: 10.1016/j.canlet.2014.07.008. Epub 2014 Jul 25.

Authors

Yan-Mei Cui¹, Dan Jiang², Shi-Hong Zhang³, Ping Wu¹, Ya-Ping Ye¹, Cui-Min Chen¹, Na Tang¹, Li Liang¹, Ting-Ting Li¹, Lu Qi¹, Shu-Yang Wang¹, Hong-Li Jiao¹, Jie Lin¹, Yan-Qing Ding¹, Wen-Ting Liao⁴

Affiliations

¹ Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, People's Republic of China; Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, People's Republic of China.
² Department of Pathology, West China Hospital, Sichuan University, Chengdu 610041, People's Republic of China.
³ Department of Laboratory Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China.
⁴ Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, People's Republic of China; Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, People's Republic of China. Electronic address: liaowt2002@gmail.com.

PMID: 25069037
DOI: 10.1016/j.canlet.2014.07.008

Abstract

Abnormal expression of FOXC2 has been found in several human cancers. However, the role of FOXC2 in the progression of colorectal cancer (CRC) has not been well characterized. In analysis of 206 CRC specimens, we revealed that both high expression and nuclear localization of FOXC2 were correlated to aggressive characteristics and poor survival of patients with CRC. FOXC2 promoted cell proliferation through activation of MAPK and AKT pathways, subsequently down-regulating p27, up-regulating cyclin D1 and p-FOXO3a. Furthermore, FOXC2 nuclear localization was required for its promotion of cell proliferation. These findings suggest that FOXC2 plays an essential role in CRC progression and may serve as a valuable clinical prognostic marker of this disease.

Keywords: Colorectal cancer; FOXC2; Nuclear localization; Prognosis; Proliferation.

Publication types

Research Support, Non-U.S. Gov't
Retracted Publication

MeSH terms

Adenocarcinoma / enzymology*
Adenocarcinoma / genetics
Adenocarcinoma / pathology
Adenocarcinoma / therapy
Adolescent
Adult
Aged
Biomarkers, Tumor / genetics
Biomarkers, Tumor / metabolism*
Caco-2 Cells
Cell Proliferation*
Colorectal Neoplasms / enzymology*
Colorectal Neoplasms / genetics
Colorectal Neoplasms / pathology
Colorectal Neoplasms / therapy
Cyclin D1 / metabolism
Cyclin-Dependent Kinase Inhibitor p27 / metabolism
Disease-Free Survival
Enzyme Activation
Female
Forkhead Box Protein O3
Forkhead Transcription Factors / genetics
Forkhead Transcription Factors / metabolism*
Gene Expression Regulation, Neoplastic
HCT116 Cells
HT29 Cells
Humans
Male
Middle Aged
Mitogen-Activated Protein Kinases / metabolism*
Proto-Oncogene Proteins c-akt / metabolism*
RNA Interference
Signal Transduction*
Time Factors
Transfection
Up-Regulation
Young Adult

Substances

Biomarkers, Tumor
CCND1 protein, human
CDKN1B protein, human
FOXO3 protein, human
Forkhead Box Protein O3
Forkhead Transcription Factors
mesenchyme fork head 1 protein
Cyclin D1
Cyclin-Dependent Kinase Inhibitor p27
Proto-Oncogene Proteins c-akt
Mitogen-Activated Protein Kinases