Adenomatous Polyposis Coli loss controls cell cycle regulators and response to paclitaxel in MDA-MB-157 metaplastic breast cancer cells

Autor: T. Murlidharan Nair, Sara M. Maloney, Monica K. VanKlompenberg, Bronwyn J. Berkeley, Emily Astarita, Jenifer R. Prosperi, Camden A. Hoover
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Cell
Cancer Treatment
Cell Cycle Proteins
Triple Negative Breast Neoplasms
Apoptosis
Biochemistry
Contractile Proteins
Animal Cells
Breast Tumors
Medicine and Health Sciences
Cell Cycle and Cell Division
RNA
Small Interfering
Post-Translational Modification
Phosphorylation
Cyclin B1
Triple-negative breast cancer
Multidisciplinary
biology
Cell Death
Cell cycle
medicine.anatomical_structure
Oncology
Cell Processes
Medicine
Female
Cellular Types
Research Article
Paclitaxel
Adenomatous polyposis coli
Immune Cells
Science
Adenomatous Polyposis Coli Protein
Immunology
Antigen-Presenting Cells
Cell Line
Tumor
Cyclins
CDC2 Protein Kinase
Breast Cancer
medicine
Humans
Antigen-presenting cell
Cyclin-dependent kinase 1
Metaplasia
Biology and Life Sciences
Cancers and Neoplasms
Proteins
Cell Biology
Actins
Cytoskeletal Proteins
Drug Resistance
Neoplasm
biology.protein
Cancer research
Cyclin-dependent kinase 6
Zdroj: PLoS ONE, Vol 16, Iss 8 (2021)
PLoS ONE
PLoS ONE, Vol 16, Iss 8, p e0255738 (2021)
ISSN: 1932-6203
Popis: Adenomatous Polyposis Coli (APC) is lost in approximately 70% of sporadic breast cancers, with an inclination towards triple negative breast cancer (TNBC). TNBC is treated with traditional chemotherapy, such as paclitaxel (PTX); however, tumors often develop drug resistance. We previously created APC knockdown cells (APC shRNA1) using the human TNBC cells, MDA-MB-157, and showed that APC loss induces PTX resistance. To understand the mechanisms behind APC-mediated PTX response, we performed cell cycle analysis and analyzed cell cycle related proteins. Cell cycle analysis indicated increased G2/M population in both PTX-treated APC shRNA1 and parental cells, suggesting that APC expression does not alter PTX-induced G2/M arrest. We further studied the subcellular localization of the G2/M transition proteins, cyclin B1 and CDK1. The APC shRNA1 cells had increased CDK1, which was preferentially localized to the cytoplasm, and increased baseline CDK6. RNA-sequencing was performed to gain a global understanding of changes downstream of APC loss and identified a broad mis-regulation of cell cycle-related genes in APC shRNA1 cells. Our studies are the first to show an interaction between APC and taxane response in breast cancer. The implications include designing combination therapy to re-sensitize APC-mutant breast cancers to taxanes using the specific cell cycle alterations.
Databáze: OpenAIRE
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