Atypical PKCs activate Vimentin to facilitate prostate cancer cell motility and invasion

Wishrawana S Ratnayake; Christopher A Apostolatos; Sloan Breedy; Clare L Dennison; Robert Hill; Mildred Acevedo-Duncan

doi:10.1080/19336918.2021.1882782

Atypical PKCs activate Vimentin to facilitate prostate cancer cell motility and invasion

Cell Adh Migr. 2021 Dec;15(1):37-57. doi: 10.1080/19336918.2021.1882782.

Authors

Wishrawana S Ratnayake¹, Christopher A Apostolatos¹, Sloan Breedy¹, Clare L Dennison², Robert Hill³, Mildred Acevedo-Duncan¹

Affiliations

¹ Department of Chemistry, University of South Florida , Tampa, FL, USA.
² Department of Integrative Biology, University of South Florida , Tampa, FL, USA.
³ Department of Cell Biology, Microbiology and Molecular Biology, University of South Florida , Tampa, FL, USA.

Abstract

Atypical protein kinase C (aPKC) are involved in progression of many human cancers. Vimentin is expressed during epithelial to mesenchymal transition (EMT). Molecular dynamics of Vimentin intermediate filaments (VIFs) play a key role in metastasis. This article is an effort to provide thorough understanding of the relationship between Vimentin and aPKCs . We demonstrate that diminution of aPKCs lead to attenuate prostate cellular metastasis through the downregulation of Vimentin expression. siRNA knocked-down SNAIL1 and PRRX1 reduce aPKC activity along with Vimentin. Results suggest that aPKCs target multiple activation sites (Ser33/39/56) on Vimentin and therefore is essential for VIF dynamics regulation during the metastasis of prostate cancer cells. Understanding the aPKC related molecular mechanisms may provide a novel therapeutic path for prostate carcinoma.

Keywords: PKC-ζ; PKC-ι; Vimentin dynamics; metastasis; phosphorylation; prostate cancer.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Line, Tumor
Cell Movement
Epithelial-Mesenchymal Transition* / genetics
Homeodomain Proteins
Humans
Intermediate Filaments
Male
Prostatic Neoplasms* / genetics
Vimentin / genetics

Substances

Homeodomain Proteins
PRRX1 protein, human
Vimentin

Grants and funding

We acknowledge the generous financial contributions from the Leo and Ann Albert Charitable Trust, The Sapphire Foundation for Prostate Cancer, the Frederick H. Leonhardt Foundation, The Daniel Tanner Foundation, Kyrias Foundation, Brotman Foundation of California, Baker Hughes Foundation, Irving S. Cooper Family Foundation, and the Creag Foundation.