Overexpression of Estrogen Receptor α in Mammary Glands of Aging Mice Is Associated with a Proliferative Risk Signature and Generation of Estrogen Receptor α–Positive Mammary Adenocarcinomas

Furth, Priscilla A.; Wang, Weisheng; Kang, Keunsoo; Rooney, Brendan; Keegan, Grace; Muralidaran, Vinona; Wong, John Chee Meng; Shearer, Charles; Zou, Xiaojun; Flaws, Jodi A.

doi:10.1016/j.ajpath.2022.09.008

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2024

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Cited by 3 publications

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“…5 (a), the subpathways are up-regulated in the high-risk group. Interestingly, overexpression of CCNB1 , MYBL2 , and ESR1 , promoting cell proliferation, can lead to higher recurrence risks [39] , [45] . To further examine the prognostic potential of the top-3 subpathways, we conducted survival analyses and a simulation study assuming a targeted therapy situation.…”

Section: Resultsmentioning

confidence: 99%

Multi-layered knowledge graph neural network reveals pathway-level agreement of three breast cancer multi-gene assays

Lee,

Park,

Piao

et al. 2024

Computational and Structural Biotechnology Journal

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Section: Resultsmentioning

confidence: 99%

Multi-layered knowledge graph neural network reveals pathway-level agreement of three breast cancer multi-gene assays

Lee,

Park,

Piao

et al. 2024

Computational and Structural Biotechnology Journal

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Mammary Gland-Endocrinology

Furth

2024

Reference Module in Biomedical Sciences

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HDAC inhibitors modulate Hippo pathway signaling in hormone positive breast cancer

Lin,

Tseng,

Lin

et al. 2024

Preprint

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Breast cancer has constantly been the leading causes of death in women, and hormone receptor (HR) positive, HER2 negative is the majority subtype. Histone deacetylase (HDAC) inhibitors have shown clinical benefit in HR (+) breast cancer patients. The hippo pathway proteins YAP/TAZ are often viewed as pro-tumorigenic, however, recent studies support a role of YAP as a tumor suppressor in HR (+) breast cancer downregulation of estrogen receptor (ER) expression. Few studies have investigated the link between HDACi and the Hippo pathway. In our study, we demonstrate that HDAC inhibitors induce transcriptional down-regulation of YAP expression, while conversely activating a TEAD mediated transcriptional program with upregulation of canonical Hippo pathway genes. We further identified 4 Hippo canonical genes (CCDC80, GADD45A, F3, TGFB2) that were upregulated by HDAC inhibitors and associated with significantly improved survival in a HR (+) breast cancer cohort. Patients with high CCDC80 or GADD45A expression had significantly better survival outcomes compared to patients with low expression. Our study provides a novel mechanism of action for the clinical benefit of HDAC inhibitors, while providing further experimental support that Hippo-TEAD transcriptional activation is associated with better outcomes in HR (+) breast cancer.

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Overexpression of Estrogen Receptor α in Mammary Glands of Aging Mice Is Associated with a Proliferative Risk Signature and Generation of Estrogen Receptor α–Positive Mammary Adenocarcinomas

Cited by 3 publications

References 72 publications

Multi-layered knowledge graph neural network reveals pathway-level agreement of three breast cancer multi-gene assays

Multi-layered knowledge graph neural network reveals pathway-level agreement of three breast cancer multi-gene assays

Mammary Gland-Endocrinology

HDAC inhibitors modulate Hippo pathway signaling in hormone positive breast cancer

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