Protein arginine methyltransferase 5 (PRMT5) and the ERK1/2 & PI3K pathways: A case for PRMT5 inhibition and combination therapies in cancer

Tzuriel Sapir, David Shifteh, Moshe Pahmer, Sanjay Goel, Radhashree Maitra

Research output: Contribution to journalReview articlepeer-review

10 Scopus citations

Abstract

The ERK1/2 (RAS, RAF, MEK, ERK) and PI3K (PI3K, AKT, mTOR, PTEN) pathways are the chief signaling pathways for cellular proliferation, survival, and differentiation. Overactivation and hyperphosphorylation of the ERK1/2 & PI3K pathways is frequently observed in cancer and is associated with poor patient prognosis. While it is well known that genetic alterations lead to the dysregulation of the ERK1/2 & PI3K pathways, increasing evidence showcase that epigenetic alterations also play a major role in the regulation of the ERK1/2 & PI3K pathways. Protein Arginine Methyltransferase 5 (PRMT5) is a posttranslational modifier for multiple cellular processes, which is currently being tested as a therapeutic target for cancer. PRMT5 has been shown to be overexpressed in many types of cancers, as well as negatively correlated with patient survival. Numerous studies are indicating that as a posttranslational modifier, PRMT5 is extensively involved in regulating the ERK1/2 & PI3K pathways. In addition, a large number of in vitro and in vivo studies are demonstrating that PRMT5 inhibition, as well as PRMT5 and ERK1/2 & PI3K combination therapies, show significant therapeutic effects in many cancer types. In this review, we explore the vast interactions that PRMT5 has with the ERK1/2 & PI3K pathways, and we make the case for further testing of PRMT5 inhibition, as well as PRMT5 and ERK1/2 & PI3K combination therapies, for the treatment of cancer.

Original languageEnglish (US)
Pages (from-to)388-394
Number of pages7
JournalMolecular Cancer Research
Volume19
Issue number3
DOIs
StatePublished - Mar 1 2021

ASJC Scopus subject areas

  • Molecular Biology
  • Oncology
  • Cancer Research

Fingerprint

Dive into the research topics of 'Protein arginine methyltransferase 5 (PRMT5) and the ERK1/2 & PI3K pathways: A case for PRMT5 inhibition and combination therapies in cancer'. Together they form a unique fingerprint.

Cite this