Inhibition Of Fasn Suppresses Migration,Invasion And Growth In Hepatoma Carcinoma Cells By Deregulating The HIF-1?/IGFBP1 Pathway

Hepatocellular carcinoma(HCC)is the second most common cause of cancer-related deaths worldwide.Due to a high propensity to metastasize,active angiogenesis and rapid proliferation,recurrence and poor prognosis are major obstacles for treatment and cure of HCC.In order to study the detailed mechanisms of how fatty acid synthase(FASN)promotes migration,invasion and healing in tumor cells.In the present study,the previous results that FASN was expressed higher in cancer samples than in non-cancerous samples(adjacent tissue),and influenced migration,invasion of hepatoma carcinoma cells,were verified by many test methods,such as immunohistochemistry,tissue microarrays,Transwell assay and wound healing assay.The secretory proteins of HBV associated hepatocellular carcinoma cells(HepG2.2.15)with or without FASN knockdown were analyzed using the iTRAQ(isobaric tags for relative and absolute quantitation)method to identify differentially expressed proteins(DEPs).Among 30 DEPs,eight were significantly upregulation,twenty-two were significantly downregulation.The DEPs were verifed by RT-PCR and western blot analysis,and were consistent with the iTRAQ results.Inhibition of FASN can decrease the levels of IGFBP1,and the expression,activity,and ubiquitination of HIF-1?.Therefore,it is convincing that inhibition of FASN can suppress migration,invasion and healing of hepatoma carcinoma cells by decreasing HIF-1?,and IGFBP1.