Fatty acid transport protein-5 (FATP5) deficiency enhances hepatocellular carcinoma progression and metastasis by reprogramming cellular energy metabolism and regulating the AMPK-mTOR signaling pathway

Abstract Aberrant lipid metabolism is an essential feature of hepatocellular carcinoma (HCC). Fatty acid transport protein-5 (FATP5) is highly expressed in the liver and is involved in the fatty acid transport pathway. However, the potential role of FATP5 in the pathogenesis of HCC remains largely u...

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Autores principales:	Ming-Da Wang, Nan-Ya Wang, Hui-Lu Zhang, Li-Yang Sun, Qiu-Ran Xu, Lei Liang, Chao Li, Dong-Sheng Huang, Hong Zhu, Tian Yang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Publishing Group 2021
Materias:	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/c58f452b6290429e9c3ff179844f4f53
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spelling	oai:doaj.org-article:c58f452b6290429e9c3ff179844f4f532021-11-14T12:16:44ZFatty acid transport protein-5 (FATP5) deficiency enhances hepatocellular carcinoma progression and metastasis by reprogramming cellular energy metabolism and regulating the AMPK-mTOR signaling pathway10.1038/s41389-021-00364-52157-9024https://doaj.org/article/c58f452b6290429e9c3ff179844f4f532021-11-01T00:00:00Zhttps://doi.org/10.1038/s41389-021-00364-5https://doaj.org/toc/2157-9024Abstract Aberrant lipid metabolism is an essential feature of hepatocellular carcinoma (HCC). Fatty acid transport protein-5 (FATP5) is highly expressed in the liver and is involved in the fatty acid transport pathway. However, the potential role of FATP5 in the pathogenesis of HCC remains largely unknown. Herein, we showed that FATP5 was downregulated in HCC tissues and even much lower in vascular tumor thrombi. Low expression of FATP5 was correlated with multiple aggressive and invasive clinicopathological characteristics and contributed to tumor metastasis and a poor prognosis in HCC patients. FATP5 inhibited the epithelial–mesenchymal transition (EMT) process and suppressed HCC cell migration and invasion, while silencing FATP5 had the opposite effects. Mechanistically, knockdown of FATP5 promoted cellular glycolytic flux and ATP production, thus suppressing AMP-activated protein kinase (AMPK) and activating its downstream signaling mammalian target of rapamycin (mTOR) to support HCC progression and metastasis. Activation of AMPK using metformin reversed the EMT program and impaired the metastatic capacity of FATP5-depleted HCC cells. Collectively, FATP5 served as a novel suppressor of HCC progression and metastasis partly by regulating the AMPK/mTOR pathway in HCC, and targeting the FATP5-AMPK axis may be a promising therapeutic strategy for personalized HCC treatment.Ming-Da WangNan-Ya WangHui-Lu ZhangLi-Yang SunQiu-Ran XuLei LiangChao LiDong-Sheng HuangHong ZhuTian YangNature Publishing GrouparticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENOncogenesis, Vol 10, Iss 11, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Ming-Da Wang Nan-Ya Wang Hui-Lu Zhang Li-Yang Sun Qiu-Ran Xu Lei Liang Chao Li Dong-Sheng Huang Hong Zhu Tian Yang Fatty acid transport protein-5 (FATP5) deficiency enhances hepatocellular carcinoma progression and metastasis by reprogramming cellular energy metabolism and regulating the AMPK-mTOR signaling pathway
description	Abstract Aberrant lipid metabolism is an essential feature of hepatocellular carcinoma (HCC). Fatty acid transport protein-5 (FATP5) is highly expressed in the liver and is involved in the fatty acid transport pathway. However, the potential role of FATP5 in the pathogenesis of HCC remains largely unknown. Herein, we showed that FATP5 was downregulated in HCC tissues and even much lower in vascular tumor thrombi. Low expression of FATP5 was correlated with multiple aggressive and invasive clinicopathological characteristics and contributed to tumor metastasis and a poor prognosis in HCC patients. FATP5 inhibited the epithelial–mesenchymal transition (EMT) process and suppressed HCC cell migration and invasion, while silencing FATP5 had the opposite effects. Mechanistically, knockdown of FATP5 promoted cellular glycolytic flux and ATP production, thus suppressing AMP-activated protein kinase (AMPK) and activating its downstream signaling mammalian target of rapamycin (mTOR) to support HCC progression and metastasis. Activation of AMPK using metformin reversed the EMT program and impaired the metastatic capacity of FATP5-depleted HCC cells. Collectively, FATP5 served as a novel suppressor of HCC progression and metastasis partly by regulating the AMPK/mTOR pathway in HCC, and targeting the FATP5-AMPK axis may be a promising therapeutic strategy for personalized HCC treatment.
format	article
author	Ming-Da Wang Nan-Ya Wang Hui-Lu Zhang Li-Yang Sun Qiu-Ran Xu Lei Liang Chao Li Dong-Sheng Huang Hong Zhu Tian Yang
author_facet	Ming-Da Wang Nan-Ya Wang Hui-Lu Zhang Li-Yang Sun Qiu-Ran Xu Lei Liang Chao Li Dong-Sheng Huang Hong Zhu Tian Yang
author_sort	Ming-Da Wang
title	Fatty acid transport protein-5 (FATP5) deficiency enhances hepatocellular carcinoma progression and metastasis by reprogramming cellular energy metabolism and regulating the AMPK-mTOR signaling pathway
title_short	Fatty acid transport protein-5 (FATP5) deficiency enhances hepatocellular carcinoma progression and metastasis by reprogramming cellular energy metabolism and regulating the AMPK-mTOR signaling pathway
title_full	Fatty acid transport protein-5 (FATP5) deficiency enhances hepatocellular carcinoma progression and metastasis by reprogramming cellular energy metabolism and regulating the AMPK-mTOR signaling pathway
title_fullStr	Fatty acid transport protein-5 (FATP5) deficiency enhances hepatocellular carcinoma progression and metastasis by reprogramming cellular energy metabolism and regulating the AMPK-mTOR signaling pathway
title_full_unstemmed	Fatty acid transport protein-5 (FATP5) deficiency enhances hepatocellular carcinoma progression and metastasis by reprogramming cellular energy metabolism and regulating the AMPK-mTOR signaling pathway
title_sort	fatty acid transport protein-5 (fatp5) deficiency enhances hepatocellular carcinoma progression and metastasis by reprogramming cellular energy metabolism and regulating the ampk-mtor signaling pathway
publisher	Nature Publishing Group
publishDate	2021
url	https://doaj.org/article/c58f452b6290429e9c3ff179844f4f53
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Fatty acid transport protein-5 (FATP5) deficiency enhances hepatocellular carcinoma progression and metastasis by reprogramming cellular energy metabolism and regulating the AMPK-mTOR signaling pathway

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