2. Academic Validation
  3. 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

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

  • Oncogenesis. 2021 Nov 12;10(11):74. doi: 10.1038/s41389-021-00364-5.
Ming-Da Wang  # 1 2,  Nan-Ya Wang  # 3,  Hui-Lu Zhang  # 4,  Li-Yang Sun 1,  Qiu-Ran Xu 1 5,  Lei Liang 1,  Chao Li 2,  Dong-Sheng Huang 6 7,  Hong Zhu 8,  Tian Yang 9 10 11
Affiliations

Affiliations

  • 1 Department of Hepatobiliary Pancreatic and Minimal Invasive Surgery, Zhejiang Provincial People's Hospital (People's Hospital of Hangzhou Medical College), Hangzhou, Zhejiang, China.
  • 2 Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China.
  • 3 The Cancer Center, the First Hospital of Jilin University, Changchun, Jilin, China.
  • 4 Department of Digestive Diseases, Huashan Hospital, Fudan University, Shanghai, China.
  • 5 School of Clinical Medicine, Hangzhou Medical College, Hangzhou, China.
  • 6 Department of Hepatobiliary Pancreatic and Minimal Invasive Surgery, Zhejiang Provincial People's Hospital (People's Hospital of Hangzhou Medical College), Hangzhou, Zhejiang, China. huangdongshengsj@hotmail.com.
  • 7 School of Clinical Medicine, Hangzhou Medical College, Hangzhou, China. huangdongshengsj@hotmail.com.
  • 8 Department of Medical Oncology, the First Affiliated Hospital of Soochow University, Suzhou, China. zhuhong_jasmine@suda.edu.cn.
  • 9 Department of Hepatobiliary Pancreatic and Minimal Invasive Surgery, Zhejiang Provincial People's Hospital (People's Hospital of Hangzhou Medical College), Hangzhou, Zhejiang, China. yangtianehbh@smmu.edu.cn.
  • 10 Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China. yangtianehbh@smmu.edu.cn.
  • 11 School of Clinical Medicine, Hangzhou Medical College, Hangzhou, China. yangtianehbh@smmu.edu.cn.
  • # Contributed equally.
PMID: 34772914 DOI: 10.1038/s41389-021-00364-5
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.

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