STC2 promotes the epithelial-mesenchymal transition of colorectal cancer cells through AKT-ERK signaling pathways.
The STC2 protein involves in carcinogenesis and progression of many cancers. It remains unclear how STC2 regulates the epithelial-mesenchymal transition (EMT) process and colorectal cancer (CRC) development. Here we systematically investigated STC2-activated early occurrence of EMT and CRC cell migration in vitro, clinical associations of STC2 with CRC development and patient survival. The secretion and expression level of STC2 were both greatly increased in EMT cells and CRC cells compared with the normal epithelial NCM460 cells. And the conditioned media from EMT cells stimulated epithelia and colon cancer cells to obtain EMT characteristics. STC2 overexpression promoted CRC cell growth and cell migration in vitro, and STC2 enhanced tumor growth in a mouse CRC-xenograft model. Corresponding to EMT marker expression changes, several critical signaling pathway molecules including pERK, pAKT, PI3K and Ras were remarkably increased either in NCM460 cells transfected with STC2 plasmids or in cells induced with exogenous STC2 protein. However blocking AKT-ERK signaling pathways attenuated STC2-activated EMT process. Furthermore the elevated STC2 expressions were also confirmed in 77 clinical tumor tissues and sera from CRC patients, and the increased STC2 in tumor tissues and sera correlated with tumor pathologic stage and poor survival for CRC patients. In conclusion, STC2 promotes CRC tumorigenesis and EMT progression through activating ERK/MEK and PI3K/AKT signaling pathways. STC2 protein is also a potential tumor biomarker for CRC diagnosis and prognosis.
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, P.R. China.
Bing
B
Chen
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, P.R. China.
Xiao
X
Zeng
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, P.R. China.
Yu
Y
He
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, P.R. China.
Xixi
X
Wang
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, P.R. China.
Ziwei
Z
Liang
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, P.R. China.
Jingjing
J
Liu
Department of Urinary Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, P. R. China.
Peng
P
Zhang
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, P.R. China.|Laboratory of Cell and Molecular Biology & State Key Laboratory of Molecular Oncology, Cancer Institute & Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, 100034, P. R. China.
Hongxia
H
Zhu
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, P.R. China.|Laboratory of Cell and Molecular Biology & State Key Laboratory of Molecular Oncology, Cancer Institute & Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, 100034, P. R. China.
Ningzhi
N
Xu
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, P.R. China.
Shufang
S
Liang
D000328:Adult; D000368:Aged; D000818:Animals; D015179:Colorectal Neoplasms / Q000401:mortality / Q000473:pathology*; D058750:Epithelial-Mesenchymal Transition; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology*; D005260:Female; D006023:Glycoproteins / Q000097:blood / Q000502:physiology*; D019073:HT29 Cells; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood / Q000502:physiology*; D020935:MAP Kinase Signaling System; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D009367:Neoplasm Staging; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D059016:Tumor Microenvironment
D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; C114997:STC2 protein, human; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases
colorectal cancer; epithelial-mesenchymal transition; stanniocalcin 2; tumor biomarker
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