title: Silencing of CerS6 increases the invasion and glycolysis of melanoma WM35, WM451 and SK28 cell lines via increased GLUT1-induced downregulation of WNT5A.
abstract: Ceramide synthases (CerSs) have been shown to regulate numerous aspects of cancer development. CerS6 has been suggested to be involved in cancer etiology. However, little is known concerning the exact effect of CerS6 on the malignant behavior of melanoma, including glycolysis, proliferation and invasion. In the present study, we found that the expression of CerS6 was low in the melanoma cell lines, including WM35, WM451 and SK-28, and the expression level was related to the malignanct behavior of the melanoma cell lines. We constructed overexpression and silencing models of CerS6 in three melanoma cell lines and found that silencing of CerS6 promoted the ability of proliferation and invasion in the melanoma cell lines. Additionally, downregulation of CerS6 upregulated the activity of glycolysis-related enzyme, and enhanced the expression of glycolysis-related genes, including GLUT1 and MCT1. Furthermore, we identified the genes whose expression levels were changed after silencing of CerS6 by gene microarray. The expression of glycolysis-related gene SLC2A1 (also known as GLUT1) was found to be upregulated, while notably WNT5A was downregulated. The altered expression of GLUT1 and WNT5A was verified by qPCR and western blotting. Furthermore, silencing of GLUT1 in the melanoma cells resulted in the increased expression of WNT5A and the decreased ability of invasion and proliferation in the melanoma cells. Collectively, silencing of CerS6 induced the increased expression of GLUT1, which downregulated the expression of WNT5A and enhanced the invasion and proliferation of melanoma cells. Thus, CerS6 may provide a novel therapeutic target for melanoma treatment.
authors.affiliation: Department of Plastic Surgery, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Department of Oncology, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China.
authors.forename: Ke
authors.initials: K
authors.lastname: Cao
authors.affiliation: Department of Oncology, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Plastic Surgery, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China.
authors.forename: Jia
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Plastic Surgery, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China.
authors.forename: Rui
authors.initials: R
authors.lastname: Liu
authors.affiliation: Department of Plastic Surgery, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China.
authors.forename: Shaohua
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Plastic Surgery, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China.
authors.forename: Jianda
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Rehabilitation, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China.
authors.forename: Huiqing
authors.initials: H
authors.lastname: Xie
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D051272:Glucose Transporter Type 1 / Q000502:physiology*; D006019:Glycolysis; D006801:Humans; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D009361:Neoplasm Invasiveness; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology; D051049:Sphingosine N-Acyltransferase / Q000235:genetics* / Q000378:metabolism; D000071818:Wnt-5a Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D051272:Glucose Transporter Type 1; D008565:Membrane Proteins; C495677:SLC2A1 protein, human; C085389:WNT5A protein, human; D000071818:Wnt-5a Protein; C506123:CERS6 protein, human; D051049:Sphingosine N-Acyltransferase