PIK3R3 induces epithelial-to-mesenchymal transition and promotes metastasis in colorectal cancer.
Class IA PI3K plays an essential role in the invasion and metastasis of cancer. However, the mechanisms and specific functions of PI3K isoforms in tumor invasion and metastasis are not fully understood. We evaluated the role of PIK3R3, a PI3K regulatory subunit encoded by the PIK3R3 gene, in colorectal cancer invasion and metastasis. Clinical specimens and cell lines data show that the expression level of PIK3R3 is associated with colorectal cancer metastasis. Overexpression of PIK3R3 increases tumor migration and invasion in vitro and promotes metastasis of colorectal cancers in vivo. Furthermore, we investigated that the overexpression of PIK3R3 depends on SNAI2, inducing significant epithelial-to-mesenchymal transition (EMT). Downregulation of PIK3R3 reverses this process, which possibly contributes to the enhanced invasive and metastasizing abilities of colorectal cancer cells. In this study, we found that PIK3R3 plays an important role in colorectal cancer metastasis and might be a potential and specific target for therapies against metastatic colorectal cancer.
Authors' Affiliation: Cancer Research Institute, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China.
Guihua
G
Wang
Authors' Affiliation: Cancer Research Institute, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China.
Xi
X
Yang
Authors' Affiliation: Cancer Research Institute, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China.
Chuan
C
Li
Authors' Affiliation: Cancer Research Institute, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China.
Xiaonian
X
Cao
Authors' Affiliation: Cancer Research Institute, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China.
Xuelai
X
Luo
Authors' Affiliation: Cancer Research Institute, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China jbhu@tjh.tjmu.edu.cn.
Junbo
J
Hu
D000818:Animals; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D015536:Down-Regulation; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D045325:HCT116 Cells; D019073:HT29 Cells; D064593:Heterografts; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014162:Transfection
C000604408:SNAI2 protein, human; C000604449:Snai2 protein, mouse; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D019869:Phosphatidylinositol 3-Kinases; C523442:PIK3R3 protein, human