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

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.

Cellular Processes

Although cells in the nervous system contain all the cellular machinery that exists in other cells throughout the body, nervous system cells have many specialized functions that present unique challenges in the maintenance of cellular functionality and homeostasis. The unique morphology of neurons demands elaborate cytoarchitecture, energy production, and cellular processing machinery that are unparalleled in other parts of the body. This chapter presents a broad overview of cellular processes related to the cytoskeleton, axonal transport, protein processing, and energy metabolism within the nervous system. Breakdowns of these intricate processes are involved in many diseases of the nervous system, which are discussed in subsequent chapters.