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Adipocyte mesenchymal transition contributes to mammary tumor progression.

Publication ,  Journal Article
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 ...
Published in: Cell Rep
September 13, 2022

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.

Duke Scholars

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Published In

Cell Rep

DOI

EISSN

2211-1247

Publication Date

September 13, 2022

Volume

40

Issue

11

Start / End Page

111362

Location

United States

Related Subject Headings

  • Tumor Microenvironment
  • Mammary Neoplasms, Animal
  • Humans
  • Female
  • Extracellular Matrix
  • Breast Neoplasms
  • Animals
  • Adipocytes
  • 31 Biological sciences
  • 1116 Medical Physiology
 

Citation

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Zhu, Q., Zhu, Y., Hepler, C., Zhang, Q., Park, J., Gliniak, C., … Scherer, P. E. (2022). Adipocyte mesenchymal transition contributes to mammary tumor progression. Cell Rep, 40(11), 111362. https://doi.org/10.1016/j.celrep.2022.111362
Zhu, Qingzhang, Yi Zhu, Chelsea Hepler, Qianbin Zhang, Jiyoung Park, Christy Gliniak, Gervaise H. Henry, et al. “Adipocyte mesenchymal transition contributes to mammary tumor progression.Cell Rep 40, no. 11 (September 13, 2022): 111362. https://doi.org/10.1016/j.celrep.2022.111362.
Zhu Q, Zhu Y, Hepler C, Zhang Q, Park J, Gliniak C, et al. Adipocyte mesenchymal transition contributes to mammary tumor progression. Cell Rep. 2022 Sep 13;40(11):111362.
Zhu, Qingzhang, et al. “Adipocyte mesenchymal transition contributes to mammary tumor progression.Cell Rep, vol. 40, no. 11, Sept. 2022, p. 111362. Pubmed, doi:10.1016/j.celrep.2022.111362.
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. Adipocyte mesenchymal transition contributes to mammary tumor progression. Cell Rep. 2022 Sep 13;40(11):111362.
Journal cover image

Published In

Cell Rep

DOI

EISSN

2211-1247

Publication Date

September 13, 2022

Volume

40

Issue

11

Start / End Page

111362

Location

United States

Related Subject Headings

  • Tumor Microenvironment
  • Mammary Neoplasms, Animal
  • Humans
  • Female
  • Extracellular Matrix
  • Breast Neoplasms
  • Animals
  • Adipocytes
  • 31 Biological sciences
  • 1116 Medical Physiology