Overexpression of MSK1 is associated with tumor aggressiveness and poor prognosis in colorectal cancer.
OBJECTIVE
Mitogen- and stress-activated protein kinase 1 (MSK1) has recently been implicated in cell proliferation and neoplastic transformation. However, the involvement of MSK1 in colorectal cancer (CRC) has not been addressed. This study aimed to evaluate the expression and potential functions of MSK1 in CRC.


METHODS
The MSK1 expression was investigated by immunohistochemistry, western blot and reverse transcription-polymerase chain reaction. The associations between clinicopathological characteristics and MSK1 expression were assessed. Kaplan-Meier analysis and Cox regression models were carried out. CRC cells with MSK1 knockdown or overexpression were generated. A range of experiments were performed to demonstrate MSK1's role in CRC.


RESULTS
MSK1 was overexpressed in 148 out of 329 CRC patients. CRC patients with high MSK1 expression had shorter overall survival than those with low MSK1 (P=0.033), especially among patients with stage III tumors (P=0.005). Knockdown of MSK1 in CRC cells suppressed cell proliferation, anchorage-independent growth, migration and invasion, and promoted 5-fluorouracil chemosensitivity and intracellular NADP+/NADPH ratio. However, overexpression of MSK1 had the opposite effects.


CONCLUSIONS
Overexpression of MSK1 is associated with poor prognosis in CRC and is connected to tumor aggressiveness. MSK1 is a potential target for new therapies and a candidate of biomarker for prognosis.
Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China; Guangdong Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China.
Xinhui
X
Fu
Department of Pathology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
Xinjuan
X
Fan
Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China; Guangdong Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China.
Jun
J
Hu
Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China; Guangdong Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China; Division of Experimental Pathology and Laboratory Medicine, Mayo Clinic, Rochester, MN, USA.
Hongzhi
H
Zou
Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China; Guangdong Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China.
Zhiting
Z
Chen
Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China; Guangdong Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China.
Qi
Q
Liu
Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China; Guangdong Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China.
Beibei
B
Ni
Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China; Guangdong Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China.
Xiaoli
X
Tan
Animal Experiment Center, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China.
Qiao
Q
Su
Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China; Guangdong Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China.
Jingxuan
J
Wang
Department of GI Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China. Electronic address: wangl9@mail.sysu.edu.cn.
Lei
L
Wang
Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China; Guangdong Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China. Electronic address: wangjpgz@126.com.
Jianping
J
Wang
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D002681:China; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D016016:Proportional Hazards Models; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult
D014408:Biomarkers, Tumor; D038744:Ribosomal Protein S6 Kinases, 90-kDa; C116919:mitogen and stress-activated protein kinase 1
Biomarkers; Chemosensitivity; Invasion; Migration