한빛사논문 | BRIC

한빛사 논문

조회737

Cedars-Sinai Medical Center

Cell Metab., 2023 May 9;S1550-4131(23)00140-7 | https://doi.org/10.1016/j.cmet.2023.04.013 Extracellular vesicles in fatty liver promote a metastatic tumor microenvironment

Zhijun Wang ^1,7,11, So Yeon Kim ^1,11, Wei Tu ^1,8,11, Jieun Kim ^1,11, Alexander Xu ^2,5,11, Yoon Mee Yang ^1,9, Michitaka Matsuda¹, Lien Reolizo ¹, Takashi Tsuchiya ¹, Sandrine Billet ^2,5, Alexandra Gangi ³, Mazen Noureddin ^1,10, Ben A. Falk ^2,5, Sungjin Kim ⁵, Wei Fan ¹, Mourad Tighiouart ⁵, Sungyong You^3,5, Michael S. Lewis ^2,4,6, Stephen J. Pandol ¹, Dolores Di Vizio ^3,5, Akil Merchant ^2,5, Edwin M. Posadas ^2,5, Neil A. Bhowmick ^2,5, Shelly C. Lu ¹, Ekihiro Seki ^1,5,12

¹Karsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
²Division of Hematology and Oncology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
³Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
⁴Department of Pathology, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
⁵Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
⁶Department of Pathology, Veterans Affairs Greater Los Angeles Health Care System, Los Angeles, CA 90073, USA
⁷Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
⁸Division of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030 China
⁹Department of Pharmacy, Kangwon National University, Chuncheon 24341, South Korea
¹⁰Houston Methodist Hospital, Houston Research Institute, Houston, TX 77030, USA
¹¹These authors contributed equally
¹²Lead contact

Corresponding author : Ekihiro Seki

Abstract

Liver metastasis is a major cause of death in patients with colorectal cancer (CRC). Fatty liver promotes liver metastasis, but the underlying mechanism remains unclear. We demonstrated that hepatocyte-derived extracellular vesicles (EVs) in fatty liver enhanced the progression of CRC liver metastasis by promoting oncogenic Yes-associated protein (YAP) signaling and an immunosuppressive microenvironment. Fatty liver upregulated Rab27a expression, which facilitated EV production from hepatocytes. In the liver, these EVs transferred YAP signaling-regulating microRNAs to cancer cells to augment YAP activity by suppressing LATS2. Increased YAP activity in CRC liver metastasis with fatty liver promoted cancer cell growth and an immunosuppressive microenvironment by M2 macrophage infiltration through CYR61 production. Patients with CRC liver metastasis and fatty liver had elevated nuclear YAP expression, CYR61 expression, and M2 macrophage infiltration. Our data indicate that fatty liver-induced EV-microRNAs, YAP signaling, and an immunosuppressive microenvironment promote the growth of CRC liver metastasis.

논문정보

형식Research article
게재일2023년 05월 (BRIC 등록일 2023-05-23)
연구진국외 연구진
분야 의약학 > 면역의학

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