Adipocyte mesenchymal transition contributes to mammary tumor progression.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Zhu, Q; Zhu, Y; Hepler, C; Zhang, Q; Park, J; Gliniak, C; Henry, GH; Crewe, C; Bu, D; Zhang, Z; Zhao, S; Morley, T; Li, N; Kim, D-S; Strand, D; Deng, Y; Robino, JJ; Varlamov, O; Gordillo, R; Kolonin, MG; Kusminski, CM; Gupta, RK; Scherer, PE

Published Date

  • September 13, 2022

Published In

Volume / Issue

  • 40 / 11

Start / End Page

  • 111362 -

PubMed ID

  • 36103820

Pubmed Central ID

  • PMC9533474

Electronic International Standard Serial Number (EISSN)

  • 2211-1247

Digital Object Identifier (DOI)

  • 10.1016/j.celrep.2022.111362


  • eng

Conference Location

  • United States