PTPRS Regulates Colorectal Cancer RAS Pathway Activity by Inactivating Erk and Preventing Its Nuclear Translocation

  • Sci Rep. 2018 Jun 18;8(1):9296. doi: 10.1038/s41598-018-27584-x.
Thomas B Davis  1 ,  Mingli Yang  1 ,  Michael J Schell  2 ,  Heiman Wang  1 ,  Le Ma  1 ,  W Jack Pledger  1  3 ,  Timothy J Yeatman  4
Affiliations
  • 1. Gibbs Cancer Center & Research Institute, 380 Serpentine Drive, Spartanburg, SC, 29303, USA.
  • 2. Department of Biostatistics and Bioinformatics, Moffitt Cancer Center & Research Institute, 12902 Magnolia Drive, Tampa, FL, 33612, USA.
  • 3. Department of Molecular Medicine, VCOM, 350 Howard Street, Spartanburg, SC, 29303, USA.
  • 4. Gibbs Cancer Center & Research Institute, 380 Serpentine Drive, Spartanburg, SC, 29303, USA. [email protected].
PMID: 29915291 DOI: 10.1038/s41598-018-27584-x
Abstract

Colorectal Cancer (CRC) growth and progression is frequently driven by Ras pathway activation through upstream growth factor receptor activation or through mutational activation of KRAS or BRAF. Here we describe an additional mechanism by which the Ras pathway may be modulated in CRC. PTPRS, a receptor-type protein tyrosine Phosphatase, appears to regulate Ras pathway activation through ERK. PTPRS modulates ERK phosphorylation and subsequent translocation to the nucleus. Native mutations in PTPRS, present in ~10% of CRC, may reduce its Phosphatase activity while increasing ERK activation and downstream transcriptional signaling.

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