RBM4-SRSF3-MAP4K4 splicing cascade modulates the metastatic signature of colorectal cancer cell

Jung Chun Lin, Yuan Chii Lee, Tse Hua Tan, Yu Chih Liang, Huai Chia Chuang, Yang C. Fann, Kory R. Johnson, Ying Ju Lin

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)

Abstract

Alternative splicing (AS) of pre-messenger (m)RNA is a pivotal mechanism in expanding proteomic diversity, which determines the functions of mammalian cells. By conducting transcriptome analyses to profile splicing events in human colorectal cancer (CRC) tissues compared to adjacent normal counterparts, we noted differential splicing profiles of serine/arginine-rich splicing factor 3 (SRSF3) and mitogen-activated protein 4 kinase 4 (MAP4K4) in cancerous tissues of CRC compared to adjacent normal tissues. In addition to SRSF3-mediated autoregulation, RNA-binding motif protein 4 (RBM4) constituted another mechanism in reprogramming the splicing profile of SRSF3. Upregulated expressions of SRSF3 in CRC cells modulated utilization of MAP4K4 exon 16 in a sequence-dependent manner. Alternatively spliced MAP4K4 variants exhibited differential effects on the phosphorylation of c-Jun N-terminal protein kinase 1 (JNK1) which subsequently modulated expression profiles of E-cadherin, N-cadherin, and vimentin, all of which are involved in the migration and invasion of CRC cells. Collectively, RBM4-SRSF3-MAP4K4 constitutes a novel mechanism for manipulating the metastasis of CRC cells through the JNK1 signaling pathway.

Original languageEnglish
Pages (from-to)259-272
Number of pages14
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1865
Issue number2
DOIs
Publication statusPublished - Feb 1 2018

Keywords

  • Alternative splicing
  • Colorectal cancer
  • MAP4K4
  • RBM4
  • SRSF3

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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