RBM5, 6, and 10 Differentially Regulate NUMB Alternative Splicing to Control Cancer Cell Proliferation

Elias G. Bechara, Endre Sebestyen, Isabella Bernardis, Eduardo Eyras, Juan Valcarcel

Research output: Contribution to journalArticlepeer-review

262 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)720-733
Number of pages14
JournalMolecular Cell
Volume52
Issue number5
DOIs
Publication statusPublished - 12 Dec 2013
Externally publishedYes

Fingerprint

Dive into the research topics of 'RBM5, 6, and 10 Differentially Regulate NUMB Alternative Splicing to Control Cancer Cell Proliferation'. Together they form a unique fingerprint.

Cite this