PAK-dependent regulation of actin dynamics in breast cancer cells

Marianne Best; Madeline E. Gale; Claire M. Wells

doi:10.1016/j.biocel.2022.106207

PAK-dependent regulation of actin dynamics in breast cancer cells

Marianne Best, Madeline E. Gale, Claire M. Wells^*

^*Corresponding author for this work

Comprehensive Cancer Centre

Research output: Contribution to journal › Article › peer-review

4 Citations (Scopus)

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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.

Original language	English
Article number	106207
Journal	International Journal of Biochemistry and Cell Biology
Volume	146
Early online date	11 Apr 2022
DOIs	https://doi.org/10.1016/j.biocel.2022.106207
Publication status	Published - 31 May 2022

Keywords

Actin cytoskeletal dynamics
Breast cancer
Cell invasion
Metastasis
Migrastatics
p21-activated kinases

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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title = "PAK-dependent regulation of actin dynamics in breast cancer cells",

abstract = "Metastatic Breast Cancer has a poor 25% survival rate and currently there are no clinical therapeutics which target metastasis. {\textquoteleft}Migrastatics{\textquoteright} 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.",

keywords = "Actin cytoskeletal dynamics, Breast cancer, Cell invasion, Metastasis, Migrastatics, p21-activated kinases",

author = "Marianne Best and Gale, {Madeline E.} and Wells, {Claire M.}",

note = "Funding Information: This work was funded by Cancer Research UK- Non clinical Training : C604/A29283 (MB) and UKRI-MRC-DTP (MG) . Publisher Copyright: {\textcopyright} 2022 The Authors",

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language = "English",

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T1 - PAK-dependent regulation of actin dynamics in breast cancer cells

AU - Best, Marianne

AU - Gale, Madeline E.

AU - Wells, Claire M.

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N2 - 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.

AB - 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.

KW - Actin cytoskeletal dynamics

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KW - Cell invasion

KW - Metastasis

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PAK-dependent regulation of actin dynamics in breast cancer cells

Abstract

Keywords

UN SDGs

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