Abstract
BackgroundFatty acid synthase (FASN) is frequently activated and overexpressed in human cancers, and plays a crucial role in the carcinogenesis of various cancers. In this study, our aims were to explore the role of FASN in regulating the “HER2-PI3K/Akt axis” activity and malignant phenotype of colorectal cancer.MethodsCaco-2 cells with a high expression of both HER2 and FASN were selected for functional characterization. Caco-2 cells were transfected with either the FASN specific RNAi plasmid or the negative control RNAi plasmid, followed by the RT-qPCR and western blot to examine the expression of FASN, HER2, PI3K and Akt. The MTT and colony formation assays were used to assess the proliferation potential. The migration was investigated by the transwell, and the apoptosis and cell cycle were assayed by the flow cytometry.ResultsNotably, the expression of FASN, HER2, PI3K and Akt were downregulated upon a silence of FASN. The proliferation was decreased after a downregulation of FASN, which was consistent with an increased apoptosis rate. The migration was also impaired in FASN-silenced cells.ConclusionA downregulation of FASN effectively inhibits the activity of “HER2-PI3K/Akt axis” and alters the malignant phenotype in colorectal cancer cells.
Highlights
Fatty acid synthase (FASN) is frequently activated and overexpressed in human cancers, and plays a crucial role in the carcinogenesis of various cancers
Plasmid selection and stable transfectional cells establishment Upon the transient transfection of four different FASN specific RNAi plasmids for 24 h (Figure 2A), the FASN mRNA expression of Caco-2 cells was 1.64 ± 0.72, Figure 3 FASN, HER2, PI3K and Akt expression of Caco-2 cells by RNA interference. (A) FASN, HER2, PI3K and Akt mRNA expression. * Compared with two control groups, P < 0.05. (B) FASN, HER2, PI3K, Akt and phosphAkt protein expression
Endogenous fatty acid biogenesis catalyzed by the lipogenic enzymes such as FASN constitutes an oncogenic stimulus that drives the normal epithelial cells progression toward malignancy [17,18]
Summary
Fatty acid synthase (FASN) is frequently activated and overexpressed in human cancers, and plays a crucial role in the carcinogenesis of various cancers. Our aims were to explore the role of FASN in regulating the “HER2-PI3K/Akt axis” activity and malignant phenotype of colorectal cancer. Fatty acid synthase (FASN) is a homodimeric multienzymatic protein which can be divided into seven functional domains that are assembled into two homodimers [1]. FASN expression maintains at a low level and its regulation is a complex process highly relying on the nutritional status and hormonal profile [4,5]. In cancer cells and pre-neoplastic lesions, FASN expression has been frequently found to be upregulated. An increased FASN expression is associated with the cancer progression, higher risk of recurrence and shorter survival in many types of cancers [6,7,8]
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