title: Fatty acid synthase regulates proliferation and migration of colorectal cancer cells via HER2-PI3K/Akt signaling pathway.
abstract: Recent evidence suggests that fatty acid synthase mediating de novo fatty acid synthesis plays a crucial role in the carcinogenesis process of various cancers. Moreover, HER2 and related PI3K/Akt signaling pathway, which links intimately with cellular metabolism, influence cancer biological behavior. However, it remains unknown whether malignant phenotype of colorectal cancer cells is regulated by the HER2-PI3K/Akt-FASN signaling pathway. In this study, Caco-2 cells were selected for functional characterization, and treated with ZSTK474, followed by RT-qPCR and Western blot assays examining PI3K, Akt, HER2, and FASN expression. The MTT and colony formation assays were used to assess proliferation. The migration was investigated by transwell, apoptosis, and cell-cycle analysis. We found that the blockade of PI3K/Akt signaling pathway by ZSTK474 treatment led to downregulation of PI3K, Akt, HER2, and FASN expression. The proliferation was decreased upon treatment which was consistent with an increased percentage of G(1) arrested cells instead of apoptosis. The migration of Caco-2 cells was also impaired by ZSTK474 treatment. Inhibition of HER2-PI3K/Akt signaling pathway suppresses FASN expression of Caco-2 cells, and inhibition of FASN expression changes malignant phenotype of Caco-2 cells.
authors.affiliation: Department of Internal Medicine, School of Medicine, Southeast University, Nanjing, Jiangsu Province, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Li
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Bu
authors.forename: Xiaoqiang
authors.initials: X
authors.lastname: Tian
authors.forename: Peng
authors.initials: P
authors.lastname: Wu
authors.forename: Lin
authors.initials: L
authors.lastname: Yang
authors.forename: Peilin
authors.initials: P
authors.lastname: Huang
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D018938:Caco-2 Cells / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D054890:Fatty Acid Synthase, Type I / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014227:Triazines / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D004791:Enzyme Inhibitors; D054890:Fatty Acid Synthase, Type I; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D018719:Erb-b2 Receptor Tyrosine Kinases; D014227:Triazines; C510150:ZSTK474; C518729:FASN protein, human; C508053:ERBB2 protein, human