title: FOXC2 promotes colorectal cancer proliferation through inhibition of FOXO3a and activation of MAPK and AKT signaling pathways.
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.
authors: 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.
authors: Yan-Mei
authors: YM
authors: Cui
authors: Department of Pathology, West China Hospital, Sichuan University, Chengdu 610041, People's Republic of China.
authors: Dan
authors: D
authors: Jiang
authors: Department of Laboratory Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China.
authors: Shi-Hong
authors: SH
authors: Zhang
authors: 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.
authors: Ping
authors: P
authors: Wu
authors: 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.
authors: Ya-Ping
authors: YP
authors: Ye
authors: 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.
authors: Cui-Min
authors: CM
authors: Chen
authors: 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.
authors: Na
authors: N
authors: Tang
authors: 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.
authors: Li
authors: L
authors: Liang
authors: 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.
authors: Ting-Ting
authors: TT
authors: Li
authors: 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.
authors: Lu
authors: L
authors: Qi
authors: 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.
authors: Shu-Yang
authors: SY
authors: Wang
authors: 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.
authors: Hong-Li
authors: HL
authors: Jiao
authors: 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.
authors: Jie
authors: J
authors: Lin
authors: 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.
authors: Yan-Qing
authors: YQ
authors: Ding
authors: 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.
authors: Wen-Ting
authors: WT
authors: Liao
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000628:therapy; D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D018938:Caco-2 Cells; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000628:therapy; D019938:Cyclin D1 / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D018572:Disease-Free Survival; D004789:Enzyme Activation; D005260:Female; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D008297:Male; D008875:Middle Aged; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D034622:RNA Interference; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C530104:CCND1 protein, human; C436291:CDKN1B protein, human; C499517:FOXO3 protein, human; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; C082078:mesenchyme fork head 1 protein; D019938:Cyclin D1; D050760:Cyclin-Dependent Kinase Inhibitor p27; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases
keywords: Colorectal cancer; FOXC2; Nuclear localization; Prognosis; Proliferation