期刊
MOLECULAR CELL
卷 52, 期 5, 页码 720-733出版社
CELL PRESS
DOI: 10.1016/j.molcel.2013.11.010
关键词
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资金
- Marie Curie postdoctoral fellowship [FP7-PEOPLE-2009-IEF]
- Consolider RNAREG [BIO2011-23920]
- Sandra Ibarra Foundation [FSI2011-035]
- Fundacion Botin
- Fundacion Botin, AICR
- Fundacion Alicia Koplowitz
- Consolider RNAREG
- Ministerio de Economia y Competitividad
- ICREA Funding Source: Custom
RBM5, a regulator of alternative splicing of apoptotic genes, and its highly homologous RBM6 and RBM10 are RNA-binding proteins frequently deleted or mutated in lung cancer. We report that RBM5/6 and RBM10 antagonistically regulate the proliferative capacity of cancer cells and display distinct positional effects in alternative splicing regulation. We identify the Notch pathway regulator NUMB as a key target of these factors in the control of cell proliferation. NUMB alternative splicing, which is frequently altered in lung cancer, can regulate colony and xenograft tumor formation, and its modulation recapitulates or antagonizes the effects of RBM5, 6, and 10 in cell colony formation. RBM10 mutations identified in lung cancer cells disrupt NUMB splicing regulation to promote cell growth. Our results reveal a key genetic circuit in the control of cancer cell proliferation.
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