Interaction between CD36 and FABP4 modulates adipocyte-induced fatty acid import and metabolism in breast cancer

Jones Gyamfi; Joo Hye Yeo; Doru Kwon; Byung Soh Min; Yoon Jin Cha; Ja Seung Koo; Joon Jeong; Jinu Lee; Junjeong Choi

doi:10.1038/s41523-021-00324-7

Interaction between CD36 and FABP4 modulates adipocyte-induced fatty acid import and metabolism in breast cancer

Jones Gyamfi, Joo Hye Yeo, Doru Kwon, Byung Soh Min, Yoon Jin Cha, Ja Seung Koo, Joon Jeong, Jinu Lee, Junjeong Choi

Research output: Contribution to journal › Article › peer-review

22 Citations (Scopus)

Abstract

Adipocytes influence breast cancer behaviour via fatty acid release into the tumour microenvironment. Co-culturing human adipocytes and breast cancer cells increased CD36 expression, with fatty acid import into breast cancer cells. Genetic ablation of CD36 attenuates adipocyte-induced epithelial-mesenchymal transition (EMT) and stemness. We show a feedforward loop between CD36 and STAT3; where CD36 activates STAT3 signalling and STAT3 binds to the CD36 promoter, regulating its expression. CD36 expression results in metabolic reprogramming, with a shift towards fatty acid oxidation. CD36 inhibition induces de novo lipogenesis in breast cancer cells. Increased CD36 expression occurs with increased FABP4 expression. We showed that CD36 directly interacts with FABP4 to regulate fatty acid import, transport, and metabolism. CD36 and FABP4 inhibition induces apoptosis in tumour cells. These results indicate that CD36 mediates fatty acid import from adipocytes into cancer cells and activates signalling pathways that drive tumour progression. Targeting CD36 may have a potential for therapy, which will target the tumour microenvironment.

Original language	English
Article number	129
Journal	npj Breast Cancer
Volume	7
Issue number	1
DOIs	https://doi.org/10.1038/s41523-021-00324-7
Publication status	Published - 2021 Dec

Bibliographical note

Funding Information:
This work was part of research projects funded by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (NRF-2017R1D1AB03033362, NRF-2018R1A6A1A03023718 and 2020R1A2C1003378). We greatly appreciate the support of Juwon Kang and Wonkyung Lee of the Laboratory of Translational Cancer Research, Department of Pharmacy, Yonsei University, who assisted in diverse ways to make this research successful.

Publisher Copyright:
© 2021, The Author(s).

All Science Journal Classification (ASJC) codes

Oncology
Radiology Nuclear Medicine and imaging
Pharmacology (medical)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/s41523-021-00324-7

Cite this

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title = "Interaction between CD36 and FABP4 modulates adipocyte-induced fatty acid import and metabolism in breast cancer",

abstract = "Adipocytes influence breast cancer behaviour via fatty acid release into the tumour microenvironment. Co-culturing human adipocytes and breast cancer cells increased CD36 expression, with fatty acid import into breast cancer cells. Genetic ablation of CD36 attenuates adipocyte-induced epithelial-mesenchymal transition (EMT) and stemness. We show a feedforward loop between CD36 and STAT3; where CD36 activates STAT3 signalling and STAT3 binds to the CD36 promoter, regulating its expression. CD36 expression results in metabolic reprogramming, with a shift towards fatty acid oxidation. CD36 inhibition induces de novo lipogenesis in breast cancer cells. Increased CD36 expression occurs with increased FABP4 expression. We showed that CD36 directly interacts with FABP4 to regulate fatty acid import, transport, and metabolism. CD36 and FABP4 inhibition induces apoptosis in tumour cells. These results indicate that CD36 mediates fatty acid import from adipocytes into cancer cells and activates signalling pathways that drive tumour progression. Targeting CD36 may have a potential for therapy, which will target the tumour microenvironment.",

author = "Jones Gyamfi and Yeo, {Joo Hye} and Doru Kwon and Min, {Byung Soh} and Cha, {Yoon Jin} and Koo, {Ja Seung} and Joon Jeong and Jinu Lee and Junjeong Choi",

note = "Funding Information: This work was part of research projects funded by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (NRF-2017R1D1AB03033362, NRF-2018R1A6A1A03023718 and 2020R1A2C1003378). We greatly appreciate the support of Juwon Kang and Wonkyung Lee of the Laboratory of Translational Cancer Research, Department of Pharmacy, Yonsei University, who assisted in diverse ways to make this research successful. Publisher Copyright: {\textcopyright} 2021, The Author(s).",

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AU - Gyamfi, Jones

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AU - Cha, Yoon Jin

AU - Koo, Ja Seung

AU - Jeong, Joon

AU - Lee, Jinu

AU - Choi, Junjeong

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PY - 2021/12

Y1 - 2021/12

N2 - Adipocytes influence breast cancer behaviour via fatty acid release into the tumour microenvironment. Co-culturing human adipocytes and breast cancer cells increased CD36 expression, with fatty acid import into breast cancer cells. Genetic ablation of CD36 attenuates adipocyte-induced epithelial-mesenchymal transition (EMT) and stemness. We show a feedforward loop between CD36 and STAT3; where CD36 activates STAT3 signalling and STAT3 binds to the CD36 promoter, regulating its expression. CD36 expression results in metabolic reprogramming, with a shift towards fatty acid oxidation. CD36 inhibition induces de novo lipogenesis in breast cancer cells. Increased CD36 expression occurs with increased FABP4 expression. We showed that CD36 directly interacts with FABP4 to regulate fatty acid import, transport, and metabolism. CD36 and FABP4 inhibition induces apoptosis in tumour cells. These results indicate that CD36 mediates fatty acid import from adipocytes into cancer cells and activates signalling pathways that drive tumour progression. Targeting CD36 may have a potential for therapy, which will target the tumour microenvironment.

AB - Adipocytes influence breast cancer behaviour via fatty acid release into the tumour microenvironment. Co-culturing human adipocytes and breast cancer cells increased CD36 expression, with fatty acid import into breast cancer cells. Genetic ablation of CD36 attenuates adipocyte-induced epithelial-mesenchymal transition (EMT) and stemness. We show a feedforward loop between CD36 and STAT3; where CD36 activates STAT3 signalling and STAT3 binds to the CD36 promoter, regulating its expression. CD36 expression results in metabolic reprogramming, with a shift towards fatty acid oxidation. CD36 inhibition induces de novo lipogenesis in breast cancer cells. Increased CD36 expression occurs with increased FABP4 expression. We showed that CD36 directly interacts with FABP4 to regulate fatty acid import, transport, and metabolism. CD36 and FABP4 inhibition induces apoptosis in tumour cells. These results indicate that CD36 mediates fatty acid import from adipocytes into cancer cells and activates signalling pathways that drive tumour progression. Targeting CD36 may have a potential for therapy, which will target the tumour microenvironment.

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Interaction between CD36 and FABP4 modulates adipocyte-induced fatty acid import and metabolism in breast cancer

Abstract

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