PAK-dependent regulation of actin dynamics in breast cancer cells. (May 2022)

• Record Type: Journal Article
• Authors: Best, Marianne; Gale, Madeline E.; Wells, Claire M.
• Is Part Of: International journal of biochemistry & cell biology. Volume 146(2022)
• Publication Date: 2022-05
• Subjects: p21-activated kinases -- Actin cytoskeletal dynamics -- Breast cancer -- Cell invasion -- Metastasis -- Migrastatics; Biochemistry -- Periodicals; Cytology -- Periodicals; Biochemistry -- Periodicals; Cell Biology -- Periodicals; Biochimie -- Périodiques; Cytologie -- Périodiques; Biochimie; Cytologie; Biochemistry; Cytology; Ressource Internet (Descripteur de forme); Périodique électronique (Descripteur de forme); Periodicals; 572.05
• DOI: 10.1016/j.biocel.2022.106207
• Languages: English
• ISSNs: 1357-2725

Abstract

Abstract: Metastatic Breast Cancer has a poor 25% survival rate and currently there are no clinical therapeutics which target metastasis. 'Migrastatics' are a new drug class which target migration pathway effector proteins in order to inhibit cancer cell invasion and metastasis. The p21-activated kinases (PAKs) are essential drivers of breast cancer cell migration and invasion through their regulation of actin cytoskeletal dynamics. Therefore, the PAKs present as attractive migrastatic candidates. Here we review how PAKs regulate distinct aspects of breast cancer actin dynamics focussing on cytoskeletal reorganisation, cell:matrix adhesion, actomyosin contractility and degradative invasion. Lastly, we discuss the introduction of PAK migrastatics into the well-honed breast cancer clinical pipeline. Highlights: The p21-activated kinases (PAKs) reside at a nexus of cell signalling pathways which promote breast cancer metastasis. PAK isoforms employ distinct functional roles specifically regulating actin dynamics to drive breast cancer cell invasion. Administration of PAK migrastatics with current anti-proliferative treatment could suppress breast cancer metastasis.