Adipocyte mesenchymal transition contributes to mammary tumor progression

Qingzhang Zhu, Yi Zhu, Chelsea Hepler, Qianbin Zhang, Jiyoung Park, Christy Gliniak, Gervaise H. Henry, Clair Crewe, Dawei Bu, Zhuzhen Zhang, Shangang Zhao, Thomas Morley, Na Li, Dae Seok Kim, Douglas Strand, Yingfeng Deng, Jacob J. Robino, Oleg Varlamov, Ruth Gordillo, Mikhail G. KoloninChristine M. Kusminski, Rana K. Gupta, Philipp E. Scherer

Producción científica: Articlerevisión exhaustiva

30 Citas (Scopus)

Resumen

Obesity is associated with increased cancer incidence and progression. However, the relationship between adiposity and cancer remains poorly understood at the mechanistic level. Here, we report that adipocytes from tumor-invasive mammary fat undergo de-differentiation to fibroblast-like precursor cells during tumor progression and integrate into the tumor microenvironment. Single-cell sequencing reveals that these de-differentiated adipocytes lose their original identities and transform into multiple cell types, including myofibroblast- and macrophage-like cells, with their characteristic features involved in immune response, inflammation, and extracellular matrix remodeling. The de-differentiated cells are metabolically distinct from tumor-associated fibroblasts but exhibit comparable effects on tumor cell proliferation. Inducing de-differentiation by Xbp1s overexpression promotes tumor progression despite lower adiposity. In contrast, promoting lipid-storage capacity in adipocytes through MitoNEET overexpression curbs tumor growth despite greater adiposity. Collectively, the metabolic interplay between tumor cells and adipocytes induces adipocyte mesenchymal transition and contributes to reconfigure the stroma into a more tumor-friendly microenvironment.

Idioma originalEnglish (US)
Número de artículo111362
PublicaciónCell Reports
Volumen40
N.º11
DOI
EstadoPublished - sept 13 2022

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

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