PMID- 34772914
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20211118
IS  - 2157-9024 (Print)
IS  - 2157-9024 (Electronic)
IS  - 2157-9024 (Linking)
VI  - 10
IP  - 11
DP  - 2021 Nov 12
TI  - 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.
PG  - 74
LID - 10.1038/s41389-021-00364-5 [doi]
LID - 74
AB  - 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.
CI  - (c) 2021. The Author(s).
FAU - Wang, Ming-Da
AU  - Wang MD
AD  - Department of Hepatobiliary Pancreatic and Minimal Invasive Surgery, Zhejiang 
      Provincial People's Hospital (People's Hospital of Hangzhou Medical College), 
      Hangzhou, Zhejiang, China.
AD  - Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, 
      Second Military Medical University (Navy Medical University), Shanghai, China.
FAU - Wang, Nan-Ya
AU  - Wang NY
AD  - The Cancer Center, the First Hospital of Jilin University, Changchun, Jilin, 
      China.
FAU - Zhang, Hui-Lu
AU  - Zhang HL
AD  - Department of Digestive Diseases, Huashan Hospital, Fudan University, Shanghai, 
      China.
FAU - Sun, Li-Yang
AU  - Sun LY
AD  - Department of Hepatobiliary Pancreatic and Minimal Invasive Surgery, Zhejiang 
      Provincial People's Hospital (People's Hospital of Hangzhou Medical College), 
      Hangzhou, Zhejiang, China.
FAU - Xu, Qiu-Ran
AU  - Xu QR
AD  - Department of Hepatobiliary Pancreatic and Minimal Invasive Surgery, Zhejiang 
      Provincial People's Hospital (People's Hospital of Hangzhou Medical College), 
      Hangzhou, Zhejiang, China.
AD  - School of Clinical Medicine, Hangzhou Medical College, Hangzhou, China.
FAU - Liang, Lei
AU  - Liang L
AD  - Department of Hepatobiliary Pancreatic and Minimal Invasive Surgery, Zhejiang 
      Provincial People's Hospital (People's Hospital of Hangzhou Medical College), 
      Hangzhou, Zhejiang, China.
FAU - Li, Chao
AU  - Li C
AD  - Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, 
      Second Military Medical University (Navy Medical University), Shanghai, China.
FAU - Huang, Dong-Sheng
AU  - Huang DS
AUID- ORCID: 0000-0001-7276-6054
AD  - 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.
AD  - School of Clinical Medicine, Hangzhou Medical College, Hangzhou, China. 
      huangdongshengsj@hotmail.com.
FAU - Zhu, Hong
AU  - Zhu H
AUID- ORCID: 0000-0001-7502-278X
AD  - Department of Medical Oncology, the First Affiliated Hospital of Soochow 
      University, Suzhou, China. zhuhong_jasmine@suda.edu.cn.
FAU - Yang, Tian
AU  - Yang T
AUID- ORCID: 0000-0002-8333-3673
AD  - 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.
AD  - Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, 
      Second Military Medical University (Navy Medical University), Shanghai, China. 
      yangtianehbh@smmu.edu.cn.
AD  - School of Clinical Medicine, Hangzhou Medical College, Hangzhou, China. 
      yangtianehbh@smmu.edu.cn.
LA  - eng
GR  - 81972726/National Natural Science Foundation of China (National Science 
      Foundation of China)/
PT  - Journal Article
DEP - 20211112
PL  - United States
TA  - Oncogenesis
JT  - Oncogenesis
JID - 101580004
PMC - PMC8589992
COIS- The authors declare no competing interests.
EDAT- 2021/11/14 06:00
MHDA- 2021/11/14 06:01
PMCR- 2021/11/12
CRDT- 2021/11/13 05:46
PHST- 2021/06/12 00:00 [received]
PHST- 2021/10/11 00:00 [accepted]
PHST- 2021/09/22 00:00 [revised]
PHST- 2021/11/13 05:46 [entrez]
PHST- 2021/11/14 06:00 [pubmed]
PHST- 2021/11/14 06:01 [medline]
PHST- 2021/11/12 00:00 [pmc-release]
AID - 10.1038/s41389-021-00364-5 [pii]
AID - 364 [pii]
AID - 10.1038/s41389-021-00364-5 [doi]
PST - epublish
SO  - Oncogenesis. 2021 Nov 12;10(11):74. doi: 10.1038/s41389-021-00364-5.