Mammary-specific expression of Trim24 establishes a mouse model of human metaplastic breast cancer-Reference-Cited by-同舟云学术

Mammary-specific expression of Trim24 establishes a mouse model of human metaplastic breast cancer

Published:2021-09-10 Issue:1 Volume:12 Page:
ISSN:2041-1723
Container-title:Nature Communications
language:en
Short-container-title:Nat Commun

Author:

Shah Vrutant V.^ORCID,Duncan Aundrietta D.^ORCID,Jiang Shiming,Stratton Sabrina A.^ORCID,Allton Kendra L.^ORCID,Yam Clinton,Jain Abhinav,Krause Patrick M.^ORCID,Lu Yue,Cai Shirong,Tu Yizheng,Zhou Xinhui,Zhang Xiaomei^ORCID,Jiang Yan,Carroll Christopher L.,Kang Zhijun,Liu Bin,Shen Jianjun,Gagea Mihai^ORCID,Manu Sebastian M.,Huo Lei,Gilcrease Michael,Powell Reid T.,Guo Lei,Stephan Clifford,Davies Peter J.,Parker-Thornburg Jan^ORCID,Lozano Guillermina^ORCID,Behringer Richard R.,Piwnica-Worms Helen^ORCID,Chang Jeffrey T.^ORCID,Moulder Stacy L.,Barton Michelle Craig^ORCID

Abstract

AbstractConditional overexpression of histone reader Tripartite motif containing protein 24 (TRIM24) in mouse mammary epithelia (Trim24COE) drives spontaneous development of mammary carcinosarcoma tumors, lacking ER, PR and HER2. Human carcinosarcomas or metaplastic breast cancers (MpBC) are a rare, chemorefractory subclass of triple-negative breast cancers (TNBC). Comparison of Trim24COE metaplastic carcinosarcoma morphology, TRIM24 protein levels and a derived Trim24COE gene signature reveals strong correlation with human MpBC tumors and MpBC patient-derived xenograft (PDX) models. Global and single-cell tumor profiling reveal Met as a direct oncogenic target of TRIM24, leading to aberrant PI3K/mTOR activation. Here, we find that pharmacological inhibition of these pathways in primary Trim24COE tumor cells and TRIM24-PROTAC treatment of MpBC TNBC PDX tumorspheres decreased cellular viability, suggesting potential in therapeutically targeting TRIM24 and its regulated pathways in TRIM24-expressing TNBC.

Funder

U.S. Department of Health & Human Services | National Institutes of Health

Publisher

Springer Science and Business Media LLC

Subject

General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry

Link

https://www.nature.com/articles/s41467-021-25650-z.pdf

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