WW domain-binding protein 2 acts as an oncogene by modulating the activity of the glycolytic enzyme ENO1 in glioma

Abstract

WW domain-binding protein 2 (WBP2) has been demonstrated as oncogenic in breast cancer. Many studies have revealed the WBP2 gene as a high-risk gene for leukoariaosis and cerebral white matter lesions is important in the pathologic stage of glioma development. This study aimed to illustrate the underlying mechanism by which WBP2 regulates the process of glioma development. The expression pattern of WBP2 in several tumor cells was determined, clarifying the carcinogenic action of WBP2 in glioma cells. Overexpression of WBP2 in glioma cells promoted cell proliferation and migration, and the number of S-phase cells, whereas the depletion of WBP2 by RNAi-mediated knockdown restrained cell growth and cell cycle progression. Upregulation of WBP2 significantly enhanced the tumorigenic ability of U251 cells in vivo. MS/GST pulldown assay identified α-enolase (ENO1) and Homer protein homolog 3 (Homer3) as novel potent interaction partners of WBP2. Knockdown of ENO1 or Homer3 allowed cell growth and migration to return to normal levels. Furthermore, in vitro and in vivo experiments indicated that the oncogenic role of WBP2 in glioma was through modulating ENO1 and glycolysis activity via the ENO1-PI3K/Akt signaling pathway. Collectively, these results reveal that WBP2 plays a vital role in the occurrence and development of glioma, indicating a target gene for glioblastoma treatment.

FGFRL1 affects chemoresistance of small‐cell lung cancer by modulating the PI3K/Akt pathway via ENO1

“…17,[19][20][21][22]25,26 The present research described above also confirmed that ENO1 is highly expressed in chemoresistant SCLC cells. 17,[19][20][21][22]25,26 The present research described above also confirmed that ENO1 is highly expressed in chemoresistant SCLC cells.…”

“…22 More importantly, some lncRNAs and proteins have been reported to interact with ENO1 to regulate its expression or activity in tumours. 19,23,24 This study is the first to show that FGFRL1 is involved in SCLC. We demonstrated that FGFRL1 was up-regulated in multidrug-resistant SCLC cells compared with the parental sensitive cells.…”

“…These results suggest that FGFRL1 potentially mediates chemoresistance of SCLC via ENO1. 19,21,25 According to the sequencing data, SCLC patients were equally separated into high, medium and low FGFRL1 expression groups. It has been confirmed that ENO1 can regulate the PI3K/AKT pathway positively.…”

“…In mammals, there are three isoforms of ENO: alpha-, beta-and gamma-enolase, and alpha-enolase (ENO1) is widely expressed in most tissues. [19][20][21] In addition, ENO1 can regulate the malignant biological functions of pulmonary artery smooth muscle cells through the AMPK/Akt signalling pathway. 18 Previous studies have indicated that ENO1 promotes malignant biological behaviour of tumour cells by activating glycolysis and the PI3K/Akt pathway in non-small-cell lung cancer and glioma cells.…”

“…18 Previous studies have indicated that ENO1 promotes malignant biological behaviour of tumour cells by activating glycolysis and the PI3K/Akt pathway in non-small-cell lung cancer and glioma cells. [19][20][21] In addition, ENO1 can regulate the malignant biological functions of pulmonary artery smooth muscle cells through the AMPK/Akt signalling pathway. 22 More importantly, some lncRNAs and proteins have been reported to interact with ENO1 to regulate its expression or activity in tumours.…”