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Cancer Cell. 2014 Sep 8;26(3):374-89. doi: 10.1016/j.ccr.2014.07.010.

The splicing factor RBM4 controls apoptosis, proliferation, and migration to suppress tumor progression.

Author information

1
Institute of Cancer Stem Cell, Second Affiliated Hospital, Cancer Center, Dalian Medical University, Dalian 116044, China; Department of Pharmacology and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA. Electronic address: yangwang@dlmedu.edu.cn.
2
Department of Pathology, First Affiliated Hospital. Dalian Medical University, Dalian 116001, China.
3
State Key Laboratory of Molecular Oncology, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100021, China.
4
Department of Pharmacology and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA.
5
Key Laboratory of Proteomics of Liaoning Province, Dalian Medical University, Dalian 116044, China.
6
Institute of Cancer Stem Cell, Second Affiliated Hospital, Cancer Center, Dalian Medical University, Dalian 116044, China.
7
Department of Pharmacology and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA. Electronic address: zefeng@med.unc.edu.

Abstract

Splicing dysregulation is one of the molecular hallmarks of cancer. However, the underlying molecular mechanisms remain poorly defined. Here we report that the splicing factor RBM4 suppresses proliferation and migration of various cancer cells by specifically controlling cancer-related splicing. Particularly, RBM4 regulates Bcl-x splicing to induce apoptosis, and coexpression of Bcl-xL partially reverses the RBM4-mediated tumor suppression. Moreover, RBM4 antagonizes an oncogenic splicing factor, SRSF1, to inhibit mTOR activation. Strikingly, RBM4 expression is decreased dramatically in cancer patients, and the RBM4 level correlates positively with improved survival. In addition to providing mechanistic insights of cancer-related splicing dysregulation, this study establishes RBM4 as a tumor suppressor with therapeutic potential and clinical values as a prognostic factor.

PMID:
25203323
PMCID:
PMC4159621
DOI:
10.1016/j.ccr.2014.07.010
[Indexed for MEDLINE]
Free PMC Article
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