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The adipocyte microenvironment and cancer

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Many epithelial tumors grow in the vicinity of or metastasize to adipose tissue. As tumors develop, crosstalk between adipose tissue and cancer cells leads to changes in adipocyte function and paracrine signaling, promoting a microenvironment that supports tumor growth. Over the last decade, it became clear that tumor cells co-opt adipocytes in the tumor microenvironment, converting them into cancer-associated adipocytes (CAA). As adipocytes and cancer cells engage, a metabolic symbiosis ensues that is driven by bi-directional signaling. Many cancers (colon, breast, prostate, lung, ovarian cancer, and hematologic malignancies) stimulate lipolysis in adipocytes, followed by the uptake of fatty acids (FA) from the surrounding adipose tissue. The FA enters the cancer cell through specific fatty acid receptors and binding proteins (e.g., CD36, FATP1) and are used for membrane synthesis, energy metabolism (β-oxidation), or lipid-derived cell signaling molecules (derivatives of arachidonic and linolenic acid). Therefore, blocking adipocyte-derived lipid uptake or lipid-associated metabolic pathways in cancer cells, either with a single agent or in combination with standard of care chemotherapy, might prove to be an effective strategy against cancers that grow in lipid-rich tumor microenvironments.

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Adenosine triphosphate


Brown adipose tissue


Cancer-associated adipocytes


Carnitine palmitoyltransferase 1A


Epithelial-mesenchymal transition


Fatty acids


Fatty acid-binding protein


Fatty acid translocase


Fatty acid transport protein


Fatty acid oxidation


Glycine amidinotransferase


High-fat diet


Metabolically activated macrophages


Redox-regulatory macrophages


Monoacylglycerol lipase




Natural killer


Patient-derived xenograft


Polyunsaturated fatty acids


Subcutaneous adipose tissue


Solute carrier family 27 member 1


Stromal vascular fraction


Tumor-associated macrophages


Tumor microenvironment


T regulatory cells


Uncoupling protein 1


Visceral adipose tissue


White adipose tissue


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This study is funded by DOD pilot award (W81XWH2110376) to Abir Mukherjee (A.M) and NIH grant (R01CA169604, R35CA264619) awarded to Ernst Lengyel (E.L). We thank Gail Isenberg for editing the manuscript. Illustrations were generated using

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Correspondence to Ernst Lengyel.

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E. L. receives research funding for preclinical ovarian cancer studies from Abbvie and Arsenal Bioscience outside of the scope of this work and is co-inventor on a patent proposing to use FABP inhibitors for ovarian cancer treatment. A. M. and A. J. B. have no conflicts to report.

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Mukherjee, A., Bilecz, A.J. & Lengyel, E. The adipocyte microenvironment and cancer. Cancer Metastasis Rev 41, 575–587 (2022).

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