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CD147 promotes melanoma cell growth via SOX4-mediated glycolytic metabolism
Abstract
Purpose: To determine the functional roles of cluster of differentiation 147 (CD147) in glycolysis in melanoma cells.
Methods: CD147 expression in melanoma tissue and adjacent normal tissue was determined using quantitative real time polymrase chain reaction (qRT-PCR) and immunohistochemistry. Cell Counting Kit-8 (CCK-8) and colony formation assays were used to evaluate cell viability and colony formation, respectively. The role of CD147 in glycolysis in melanoma cells was investigated by determining glucose uptake, production of lactate, and cellular level of ATP.
Results: CD147 was enhanced more in melanoma tissue than that in the adjacent normal tissue (p < 0.001). CD147 overexpression promoted the viability and colony formation of melanoma cells. On the other hand, CD147 silencing decreased the viability and colony formation of melanoma cells. Glucose uptake, production of lactate, and cellular level of ATP were upregulated in melanoma cells by CD147 overexpression and downregulated by shRNA-mediated depletion of CD147. CD147 increased expression of C-X-C motif chemokine ligand 1 (CXCL1) to activate the sex-determining region Y-related high-mobility group box 4 (SOX4) pathway. Knockdown of CXCL1 attenuated the positive regulatory effect of CD147 on SOX4. Besides, overexpression of SOX4 reversed the suppressive effects of CD147 silencing on melanoma cell viability, colony formation, and glycolysis.
Conclusion: CD147 contributes to melanoma cell growth via upregulation of SOX-mediated glycolysis, thus providing a therapeutic avenue for the management of melanoma.
Keywords: Cluster of differentiation 147, CD147, Sex-determining region Y-related high-mobility group box 4, Melanoma, Cell growth, Glycolysis
