MRCKα Is Dispensable for Breast Cancer Development in the MMTV-PyMT Model

Mei Qi Kwa; Rafael Brandao; Trong H Phung; Jianfeng Ge; Giuseppe Scieri; Cord Brakebusch

doi:10.3390/cells10040942

MRCKα Is Dispensable for Breast Cancer Development in the MMTV-PyMT Model

Cells. 2021 Apr 19;10(4):942. doi: 10.3390/cells10040942.

Authors

Mei Qi Kwa¹, Rafael Brandao¹, Trong H Phung^{1

2}, Jianfeng Ge^{1

3}, Giuseppe Scieri¹, Cord Brakebusch¹

Affiliations

¹ Biotech Research and Innovation Center (BRIC), University of Copenhagen, Ole Maaløes vej 5, 2200 Copenhagen, Denmark.
² Centre College, 600 W Walnut St, Danville, KY 40422, USA.
³ Medical Research Centre (MRC) Cancer Unit, Hutchison/MRC Research Centre, University of Cambridge, P.O. Box 197, Biomedical Campus, Cambridge CB2 0XZ, UK.

Abstract

MRCKα is a ubiquitously expressed serine/threonine kinase involved in cell contraction and F-actin turnover, which is highly amplified in human breast cancer and part of a gene expression signature for bad prognosis. Nothing is known about the in vivo function of MRCKα. To explore MRCKα function in development and in breast cancer, we generated mice lacking a functional MRCKα gene. Mice were born close to the Mendelian ratio and showed no obvious phenotype including a normal mammary gland formation. Assessing breast cancer development using the transgenic MMTV-PyMT mouse model, loss of MRCKα did not affect tumor onset, tumor growth and metastasis formation. Deleting MRCKα and its related family member MRCKβ in two triple-negative breast cancer cell lines resulted in reduced invasion of MDA-MB-231 cells, but did not affect migration of 4T1 cells. Further genomic analysis of human breast cancers revealed that MRCKα is frequently co-amplified with the oncogenes ARID4B and AKT3 which might contribute to the prognostic value of MRCKα expression. Collectively, these data suggest that MRCKα might be a prognostic marker for breast cancer, but probably of limited functional importance.

Keywords: MRCK; breast cancer; invasion.

Publication types

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

MeSH terms

Actin Depolymerizing Factors / metabolism
Actins / metabolism
Animals
Antigens, Neoplasm / metabolism
Antigens, Polyomavirus Transforming / metabolism*
Base Sequence
Carcinogenesis / drug effects
Carcinogenesis / metabolism
Carcinogenesis / pathology*
Cell Line, Tumor
Cell Survival / drug effects
Collagen / pharmacology
Disease Models, Animal
Female
Gels / pharmacology
Humans
Mammary Glands, Animal / pathology
Mammary Neoplasms, Animal / genetics
Mammary Neoplasms, Animal / metabolism*
Mammary Tumor Virus, Mouse / drug effects
Mammary Tumor Virus, Mouse / physiology*
Mice
Mice, Knockout
Mutation / genetics
Myosins / metabolism
Myotonin-Protein Kinase / metabolism*
Neoplasm Invasiveness
Neoplasm Metastasis
Neoplasm Proteins / metabolism
Phenotype
Phosphorylation / drug effects
Polymerization / drug effects
Protein Serine-Threonine Kinases / metabolism*
Proto-Oncogene Proteins c-akt / metabolism
Triple Negative Breast Neoplasms / pathology

Substances

ARID4B protein, human
Actin Depolymerizing Factors
Actins
Antigens, Neoplasm
Antigens, Polyomavirus Transforming
Gels
Neoplasm Proteins
Collagen
CDC42BPA protein, human
CDC42BPB protein, human
AKT3 protein, human
Cdc42bpa protein, mouse
Myotonin-Protein Kinase
Protein Serine-Threonine Kinases
Proto-Oncogene Proteins c-akt
Myosins

Grants and funding

703589/Horizon 2020