SIX4 promotes metastasis via activation of the PI3K-AKT pathway in colorectal cancer

Guodong Li; Fuqing Hu; Xuelai Luo; Junbo Hu; Yongdong Feng

doi:10.7717/peerj.3394

SIX4 promotes metastasis via activation of the PI3K-AKT pathway in colorectal cancer

PeerJ. 2017 May 30:5:e3394. doi: 10.7717/peerj.3394. eCollection 2017.

Authors

Guodong Li¹, Fuqing Hu¹, Xuelai Luo¹, Junbo Hu¹, Yongdong Feng¹

Affiliation

¹ Cancer Research Institute, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei, China.

Abstract

Background: Several studies report aberrant expression of sine oculis homeobox (SIX) homolog family members during cancer development and progression. SIX4 participates in organ development, such as myogenesis and neurogenesis. However, the expression and clinical implication of SIX4 in colorectal cancer (CRC) remains unclear.

Methods: The SIX4 expression levels in colorectal patients were assessed in nine different human cancer arrays and compared using patient survival data. SIX4 expression was silenced in two cell culture lines for invasion and wound healing assessment. Finally, bioinformatics assessments ascertained the pathways impacted by SIX4.

Results: SIX4 was upregulated in The Cancer Genome Atlas CRC cohort and other gene expression omnibus (GEO) cohorts. In addition, SIX4 expression significantly correlated with lymph node metastasis and advanced Tumor Node Metastasis (TNM) stages. Moreover, SIX4 overexpression was related to unfavorable prognosis in CRC patients. Silencing SIX4 inhibited CRC cell metastasis by surpressing AKT phosphorylation.

Discussion: SIX4 is upregulated in CRC and can be used as a prognosis biomarker.

Keywords: Colorectal cancer; GEO; PI3K-AKT pathway; SIX4; TCGA.

Grants and funding

This study was supported by the National Natural Science Foundation (Nos. 81372323 and 81372662). The funders had no role in study design, data collection and analysis, decision to publish, and or preparation of the manuscript.