RNase L is a negative regulator of cell migration

Shuvojit Banerjee, Geqiang Li, Yize Li, Christina Gaughan, Danika Baskar, Yvonne Parker, Daniel J. Lindner, Susan R. Weiss, Robert H. Silverman

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

RNase L is a regulated endoribonuclease that functions in the interferon antiviral response. Activation of RNase L by 2', 5'-oligoadenylates has been linked to apoptosis, autophagy and inflammation. Genetic studies have also suggested the possible involvement of the RNase L gene (RNASEL) on chromosome 1q25.3 in several types of cancer. Here we report that ablation of RNase L in human prostate cancer PC3 cells by CRISPR/Cas9 gene editing technology enhanced cell migration as determined both by transwell assays and scratch wound healing assays. In addition, RNase L knockdown by means of RNAi increased migration of PC3 and DU145 cells in response to either fibronectin or serum stimulation, as did homozygous disruption of the RNase L gene in mouse embryonic fibroblasts. Serum or fibronectin stimulation of focal adhesion kinase (FAK) autophosphorylation on tyrosine-397 was increased by either knockdown or ablation of RNase L. In contrast, a missense mutant RNase L (R667A) lacking catalytic activity failed to suppress cell migration in PC3 cells. However, a nuclease-inactive mutant mouse RNase L (W630A) was able to partially inhibit migration of mouse fibroblasts. Consistent with a role for the catalytic activity of RNase L, transfection of PC3 cells with the RNase L activator, 2', 5'-oligoadenylate, suppressed cell migration. RNase L knockdown in PC3 cells enhanced tumor growth and metastasis following implantation in the mouse prostate. Our results suggest that naturally occurring mutations in the RNase L gene might promote enhanced cell migration and metastasis.

Original languageEnglish (US)
Pages (from-to)44360-44372
Number of pages13
JournalOncotarget
Volume6
Issue number42
DOIs
StatePublished - 2015
Externally publishedYes

Keywords

  • FAK
  • Metastasis
  • Migration
  • Prostate cancer
  • RNase L

ASJC Scopus subject areas

  • Oncology

Fingerprint

Dive into the research topics of 'RNase L is a negative regulator of cell migration'. Together they form a unique fingerprint.

Cite this