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Adenomatous Polyposis Coli Loss Controls Cell Cycle Regulators And Response To Paclitaxel

Emily M. Astarita, Camden A. Hoover, Sara M. Maloney, T. M. Nair, Jenifer R Prosperi
Published 2020 · Biology

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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 PTX-treated APC shRNA1 cells compared to PTX-treated controls, 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 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.
This paper references
10.1038/346379A0
Triggering of cyclin degradation in interphase extracts of amphibian eggs by cdc2 kinase
M. Félix (1990)
Taxol (paclitaxel): mechanisms of action. Annals of oncology
(1994)
Taxol (paclitaxel): mechanisms of action. Annals of oncology : official journal of the European Society for Medical Oncology
SB Horwitz (1994)
10.1073/PNAS.160016897
Down-regulation of p21WAF1/CIP1 or p27Kip1 abrogates antiestrogen-mediated cell cycle arrest in human breast cancer cells.
S. Cariou (2000)
10.1038/35070129
Mutations in the APC tumour suppressor gene cause chromosomal instability
R. Fodde (2001)
10.1038/35070123
A role for the Adenomatous Polyposis Coli protein in chromosome segregation
K. Kaplan (2001)
10.1038/sj.onc.1204814
Protection against chemotherapy-induced cytotoxicity by cyclin-dependent kinase inhibitors (CKI) in CKI-responsive cells compared with CKI-unresponsive cells
Mathias Schmidt (2001)
10.1093/emboj/cdg627
Mitotic regulation of the human anaphase‐promoting complex by phosphorylation
C. Kraft (2003)
10.1023/A:1016074309582
Overexpression of cyclin D1 enhances taxol induced mitotic death in MCF7 cells
R. Michalides (2004)
10.1186/bcr918
Reduced expression of p27 is a novel mechanism of docetaxel resistance in breast cancer cells
I. Brown (2004)
10.1158/1535-7163.MCT-04-0282
Cyclin A–associated kinase activity is needed for paclitaxel sensitivity
Takeshi Takahashi (2005)
Cyclin Aassociated kinase activity is needed for paclitaxel sensitivity. Molecular cancer therapeutics
T Takahashi (2005)
10.1007/978-1-59745-035-5_18
Resistance To Taxanes
L. Greenberger (2006)
10.1016/j.neulet.2006.03.023
Cellular stress increases RGS2 mRNA and decreases RGS4 mRNA levels in SH-SY5Y cells
L. Song (2006)
SD: Resistance To Taxanes. In: Cancer Drug Resistance Cancer Drug Discovery and Development edn
L. M. Greenberger (2006)
10.1242/jcs.03485
Adenomatous polyposis coli (APC): a multi-functional tumor suppressor gene
K. Aoki (2007)
10.1016/J.HUMPATH.2006.09.014
Cytoplasmic localization of p27 (cyclin-dependent kinase inhibitor 1B/KIP1) in colorectal cancer: inverse correlations with nuclear p27 loss, microsatellite instability, and CpG island methylator phenotype.
S. Ogino (2007)
10.1186/bcr2231
Prediction of paclitaxel sensitivity by CDK1 and CDK2 activity in human breast cancer cells
S. Nakayama (2008)
10.1017/S1462399408000744
p21 and p27: roles in carcinogenesis and drug resistance
A. Abukhdeir (2008)
10.1038/sj.bjc.6604705
Aberrant methylation of the Adenomatous Polyposis Coli (APC) gene promoter is associated with the inflammatory breast cancer phenotype
I. Van der Auwera (2008)
BH: P21 and p27: roles in carcinogenesis and drug resistance
AM Abukhdeir (2008)
10.1007/978-0-387-98141-3
ggplot2 - Elegant Graphics for Data Analysis
H. Wickham (2009)
10.1007/978-1-4419-1145-2_6
Role of APC and its binding partners in regulating microtubules in mitosis.
Shirin Bahmanyar (2009)
10.1158/0008-5472.CAN-08-3564
Breast cancer migration and invasion depend on proteasome degradation of regulator of G-protein signaling 4.
Yan Xie (2009)
10.1038/nprot.2009.97
Mapping identifiers for the integration of genomic datasets with the R/Bioconductor package biomaRt
S. Durinck (2009)
10.1038/onc.2010.373
Defining the role of APC in the mitotic spindle checkpoint in vivo: APC-deficient cells are resistant to Taxol
S. Radulescu (2010)
10.1128/MCB.01418-09
The Embryonic Transcription Cofactor LBH Is a Direct Target of the Wnt Signaling Pathway in Epithelial Development and in Aggressive Basal Subtype Breast Cancers
Megan E. Rieger (2010)
10.1007/s10549-011-1864-9
Paclitaxel sensitivity of breast cancer cells requires efficient mitotic arrest and disruption of Bcl-xL/Bak interaction
M. L. Flores (2011)
10.1093/jnci/djr280
The role of p27(Kip1) in dasatinib-enhanced paclitaxel cytotoxicity in human ovarian cancer cells.
X. Le (2011)
10.1038/onc.2011.148
miR-135a contributes to paclitaxel resistance in tumor cells both in vitro and in vivo
A. Holleman (2011)
Zetter BR: miR-135a contributes to paclitaxel resistance in tumor cells both in vitro and in vivo
A Holleman (2011)
10.1111/j.1349-7006.2011.02131.x
Subtype‐specific alterations of the Wnt signaling pathway in breast cancer: Clinical and prognostic significance
N. Mukherjee (2012)
10.1186/gb-2013-14-4-r36
TopHat2: accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions
Daehwan Kim (2012)
10.1038/nmeth.1923
Fast gapped-read alignment with Bowtie 2
B. Langmead (2012)
10.1158/0008-5472.CAN-13-0940
Contribution of Bcl-2 phosphorylation to Bak binding and drug resistance.
Haiming Dai (2013)
10.1038/onc.2012.137
Suppression of proinvasive RGS4 by mTOR inhibition optimizes glioma treatment
M. Weiler (2013)
10.7314/APJCP.2014.15.20.8617
Roles of the Bcl-2/Bax ratio, caspase-8 and 9 in resistance of breast cancer cells to paclitaxel.
Simin Sharifi (2014)
10.1186/s13059-014-0550-8
Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2
M. Love (2014)
10.1093/carcin/bgv140
Restoration of paclitaxel resistance by CDK1 intervention in drug-resistant ovarian cancer.
Taejeong Bae (2015)
10.1186/s12885-015-1456-x
APC selectively mediates response to chemotherapeutic agents in breast cancer
M. K. VanKlompenberg (2015)
10.1016/j.bbrc.2015.11.110
Regulator of G-protein signaling 4: A novel tumor suppressor with prognostic significance in non-small cell lung cancer.
Chuanle Cheng (2016)
10.1186/s12935-016-0297-2
Analysing the mutational status of adenomatous polyposis coli (APC) gene in breast cancer
Ya-Sian Chang (2016)
10.3892/ol.2017.6009
Growth inhibition of human breast carcinoma cells by overexpression of regulator of G-protein signaling 4.
Hyun-Jung Park (2017)
10.4049/jimmunol.1700719
Regulation of the Cell Cycle and Inflammatory Arthritis by the Transcription Cofactor LBH Gene
S. Matsuda (2017)
10.18632/oncotarget.20825
Regulator of G protein signaling 4 inhibits human melanoma cells proliferation and invasion through the PI3K/AKT signaling pathway
X. Xue (2017)
10.18632/oncotarget.17848
Prolonged mitotic arrest induced by Wee1 inhibition sensitizes breast cancer cells to paclitaxel
C. W. Lewis (2017)



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