Overexpression of MSK1 is associated with tumor aggressiveness and poor prognosis in colorectal cancer

Xinhui Fu, Xinjuan Fan, Jun Hu, Hongzhi Zou, Zhiting Chen, Qi Liu, Beibei Ni, Xiaoli Tan, Qiao Su, Jingxuan Wang, Lei Wang, Jianping Wang

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Background/Aims 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.

Original languageEnglish (US)
Pages (from-to)683-691
Number of pages9
JournalDigestive and Liver Disease
Volume49
Issue number6
DOIs
StatePublished - Jun 1 2017

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Colorectal Neoplasms
Neoplasms
NADP
mitogen and stress-activated protein kinase 1
Cell Proliferation
Proportional Hazards Models
Fluorouracil
Reverse Transcription
Biomarkers
Western Blotting
Immunohistochemistry
Regression Analysis
Polymerase Chain Reaction
Survival

Keywords

  • Biomarkers
  • Chemosensitivity
  • Invasion
  • Migration

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

Cite this

Overexpression of MSK1 is associated with tumor aggressiveness and poor prognosis in colorectal cancer. / Fu, Xinhui; Fan, Xinjuan; Hu, Jun; Zou, Hongzhi; Chen, Zhiting; Liu, Qi; Ni, Beibei; Tan, Xiaoli; Su, Qiao; Wang, Jingxuan; Wang, Lei; Wang, Jianping.

In: Digestive and Liver Disease, Vol. 49, No. 6, 01.06.2017, p. 683-691.

Research output: Contribution to journalArticle

Fu, X, Fan, X, Hu, J, Zou, H, Chen, Z, Liu, Q, Ni, B, Tan, X, Su, Q, Wang, J, Wang, L & Wang, J 2017, 'Overexpression of MSK1 is associated with tumor aggressiveness and poor prognosis in colorectal cancer', Digestive and Liver Disease, vol. 49, no. 6, pp. 683-691. https://doi.org/10.1016/j.dld.2017.02.009
Fu, Xinhui ; Fan, Xinjuan ; Hu, Jun ; Zou, Hongzhi ; Chen, Zhiting ; Liu, Qi ; Ni, Beibei ; Tan, Xiaoli ; Su, Qiao ; Wang, Jingxuan ; Wang, Lei ; Wang, Jianping. / Overexpression of MSK1 is associated with tumor aggressiveness and poor prognosis in colorectal cancer. In: Digestive and Liver Disease. 2017 ; Vol. 49, No. 6. pp. 683-691.
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abstract = "Background/Aims 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.",
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AU - Fu, Xinhui

AU - Fan, Xinjuan

AU - Hu, Jun

AU - Zou, Hongzhi

AU - Chen, Zhiting

AU - Liu, Qi

AU - Ni, Beibei

AU - Tan, Xiaoli

AU - Su, Qiao

AU - Wang, Jingxuan

AU - Wang, Lei

AU - Wang, Jianping

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N2 - Background/Aims 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.

AB - Background/Aims 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.

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