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Loss of ANCO1 repression at AIB1/YAP targets drives breast cancer progression.
EMBO Rep 2020; 21(1):e48741ER

Abstract

Transcription factors critical for the transition of normal breast epithelium to ductal carcinoma in situ (DCIS) and invasive breast cancer are not clearly defined. Here, we report that the expression of a subset of YAP-activated and YAP-repressed genes in normal mammary and early-stage breast cancer cells is dependent on the nuclear co-activator AIB1. Gene expression, sequential ChIP, and ChIP-seq analyses show that AIB1 and YAP converge upon TEAD for transcriptional activation and repression. We find that AIB1-YAP repression of genes at the 1q21.3 locus is mediated by AIB1-dependent recruitment of ANCO1, a tumor suppressor whose expression is progressively lost during breast cancer progression. Reducing ANCO1 reverts AIB1-YAP-dependent repression, increases cell size, and enhances YAP-driven aberrant 3D growth. Loss of endogenous ANCO1 occurs during DCIS xenograft progression, a pattern associated with poor prognosis in human breast cancer. We conclude that increased expression of AIB1-YAP co-activated targets coupled with a loss of normal ANCO1 repression is critical to patterns of gene expression that mediate malignant progression of early-stage breast cancer.

Authors+Show Affiliations

Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA.Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA.Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA.Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA.Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA.Department of Molecular Medicine, Goethe University, Frankfurt am Main, Germany.Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA.Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA.Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA.Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31788936

Citation

Kushner, Max H., et al. "Loss of ANCO1 Repression at AIB1/YAP Targets Drives Breast Cancer Progression." EMBO Reports, vol. 21, no. 1, 2020, pp. e48741.
Kushner MH, Ory V, Graham GT, et al. Loss of ANCO1 repression at AIB1/YAP targets drives breast cancer progression. EMBO Rep. 2020;21(1):e48741.
Kushner, M. H., Ory, V., Graham, G. T., Sharif, G. M., Kietzman, W. B., Thevissen, S., ... Riegel, A. T. (2020). Loss of ANCO1 repression at AIB1/YAP targets drives breast cancer progression. EMBO Reports, 21(1), pp. e48741. doi:10.15252/embr.201948741.
Kushner MH, et al. Loss of ANCO1 Repression at AIB1/YAP Targets Drives Breast Cancer Progression. EMBO Rep. 2020 Jan 7;21(1):e48741. PubMed PMID: 31788936.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Loss of ANCO1 repression at AIB1/YAP targets drives breast cancer progression. AU - Kushner,Max H, AU - Ory,Virginie, AU - Graham,Garrett T, AU - Sharif,Ghada M, AU - Kietzman,William B, AU - Thevissen,Sophia, AU - Yuan,Meng, AU - Schmidt,Marcel O, AU - Wellstein,Anton, AU - Riegel,Anna T, Y1 - 2019/12/02/ PY - 2019/06/25/received PY - 2019/10/28/revised PY - 2019/11/12/accepted PY - 2021/01/07/pmc-release PY - 2019/12/4/pubmed PY - 2019/12/4/medline PY - 2019/12/3/entrez KW - 1q21.3 KW - AIB1 KW - ANCO1 KW - YAP KW - ductal carcinoma in situ SP - e48741 EP - e48741 JF - EMBO reports JO - EMBO Rep. VL - 21 IS - 1 N2 - Transcription factors critical for the transition of normal breast epithelium to ductal carcinoma in situ (DCIS) and invasive breast cancer are not clearly defined. Here, we report that the expression of a subset of YAP-activated and YAP-repressed genes in normal mammary and early-stage breast cancer cells is dependent on the nuclear co-activator AIB1. Gene expression, sequential ChIP, and ChIP-seq analyses show that AIB1 and YAP converge upon TEAD for transcriptional activation and repression. We find that AIB1-YAP repression of genes at the 1q21.3 locus is mediated by AIB1-dependent recruitment of ANCO1, a tumor suppressor whose expression is progressively lost during breast cancer progression. Reducing ANCO1 reverts AIB1-YAP-dependent repression, increases cell size, and enhances YAP-driven aberrant 3D growth. Loss of endogenous ANCO1 occurs during DCIS xenograft progression, a pattern associated with poor prognosis in human breast cancer. We conclude that increased expression of AIB1-YAP co-activated targets coupled with a loss of normal ANCO1 repression is critical to patterns of gene expression that mediate malignant progression of early-stage breast cancer. SN - 1469-3178 UR - https://www.unboundmedicine.com/medline/citation/31788936/Loss_of_ANCO1_repression_at_AIB1/YAP_targets_drives_breast_cancer_progression L2 - https://doi.org/10.15252/embr.201948741 DB - PRIME DP - Unbound Medicine ER -