LPLUNC1 reduces glycolysis in nasopharyngeal carcinoma cells through the PHB1‐p53/c‐Myc axis

Abstract

Cancer cells usually prefer glycolysis to support their proliferation. Our previous studies have shown that the long palate, lung, and nasal epithelial cell clone 1 (LPLUNC1) can up-regulate prohibitin 1 (PHB1) expression to inhibit the proliferation of nasopharyngeal carcinoma (NPC) cells. Given that PHB1 is an important regulator of cell energy metabolism, we explored whether and how LPLUNC1 regulated glucose glycolysis in NPC cells. LPLUNC1 or PHB1 over-expression decreased glycolysis and increased oxidative phosphorylation (OXPHOS)-related protein expression in NPC cells, accompanied by enhancing PHB1 and 14-3-3σ expression and promoting phosphorylated PHB1 nuclear translocation. Coimmunoprecipitation indicated that 14-3-3σ directly interacted with phosphorylated PHB1. PHB1 Y259A mutant over-expression abrogated the decreasing glycolysis and increasing OXPHOS-related protein expression induced by LPLUNC1 over-expression in NPC cells. LPLUNC1 over-expression also increased p53, but decreased c-Myc expression in NPC cells, which were crucial for the decrease in glycolysis and increase in OXPHOS-related protein expression induced by LPLUNC1 over-expression. Finally, we found that treatment with all-trans retinoic acid (ATRA) reduced the viability and clonogenicity of NPC cells, decreased glycolysis and increased OXPHOS-related protein xpression by enhancing LPLUNC1 expression in NPC cells. Therefore, the LPLUNC1-PHB1-p53/c-Myc axis decreased glycolysis in NPC cells and ATRA up-regulated LPLUNC1 expression, a promising drug for intervention of NPC.

ARHGAP44-mediated regulation of the p53/C-myc/Cyclin D1 pathway in modulating the malignant biological behavior of osteosarcoma cells

“…However, the roles of the ARHGAP44 / p53 and C-Myc / Cyclin D1 pathways in osteosarcoma remain unclear. The present study revealed that C-myc and Cyclin D1 may be inhibited by the downregulation of ARHGAP44 and upregulation of p53 expression levels, which is consistent with the findings of Oyang and Yenmis et al [ 33 , 34 ]. These results suggest that the downregulation of ARHGAP44 expression may inhibit the proliferation, invasion, and migration of osteosarcoma tumor cells through the p53 / C-myc / Cyclin D1 pathway (Fig.…”

“…There is also a regulatory relationship between p53 , C-myc , and Cyclin D1 . Oyang et al [ 33 ] found that LPLUNC1 reduces the proliferation of nasopharyngeal carcinoma tumor cells through the p53 / C-myc pathway. In breast cancer, metformin reduces the expression of Cyclin D1 by upregulating the p53 expression, thereby promoting tumor apoptosis [ 34 ].…”

TOM40 regulates the progression of nasopharyngeal carcinoma through ROS-mediated AKT/mTOR and p53 signaling

“…5 C, TOM40 knockdown decreased the levels of phosphorylated AKT, mTOR, p70S6K, pS6 and 4E-BP1, suggesting inactivation of the AKT/mTOR signaling pathway. The p53/p21 pathway acts downstream of ROS signaling in NPC cells and is known to trigger apoptosis [ 16 , 22 ]. We found that inhibition of TOM40 increased p21 and p53 levels, along with that of cleaved PARP and cleaved caspase 3, which lie downstream of p53 signaling.…”