MUC16 promotes EOC proliferation by regulating GLUT1 expression

Abstract

As a common malignancy in females with a higher incidence rate, epithelial ovarian cancer (EOC) is a heterogeneous disease with complexity and diversity in histology and therapeutic response. Although great progress has been made in diagnosis and therapeutic strategies, novel therapeutic strategies are required to improve survival. Although the promoting effect of mucin 16 (MUC16) on tumour progression has been reported, the potential mechanisms remain unclear. In our study, we reported that overexpression of MUC16 was significantly related to cell proliferation and disease progression in EOC. Results from clinical specimen analysis and cell experiment support this conclusion. Patients with a high MUC16 expression usually had a worse prognosis that those with a low expression. Cell proliferation ability was significantly decreased in EOC cell lines when the knockdown of MUC16. Further study shows that the function of MUC16 in cell proliferation is based on the regulation of glucose transporter 1 (GLUT1) expression. MUC16 can control glucose uptake by regulating GLUT1 in EOC cells, thereby promoting glycogen synthesis, so that tumour cells produce more energy for proliferation. This conclusion is based on two findings. First, the significant correlation between MUC16 and GLUT1 was verified by clinical specimen and TCGA data analysis. Then, alteration of MUC16 expression levels can affect the expression of GLUT1 and glucose uptake was also verified. Finally, this conclusion is further verified in vivo by tumour‐bearing mice model. To summarize, our results suggest that MUC16 promotes EOC proliferation and disease progression by regulating GLUT1 expression.

MUC16: clinical targets with great potential

“…Muc16 predicts a poor prognosis in EOC [ 23 ]. Discontinuous patterns of congestive intrarenal venous flow (IRVF) (biphasic and uniphasic) predict adverse outcomes in acute heart failure (AHF), which is difficult to detect in patients with severe symptoms.…”

“…MUC16 enhances glucose uptake by tumor cells by promoting the expression of glucose transporter 1 (GLUT1), a glucose transporter that promotes the transport of glucose molecules across cell membranes, and promotes glycogen synthesis, thus enabling tumor cells to produce more energy for proliferation [ 23 ]. The effect of MUC16 on the inhibition of anti-apoptotic B-cell lymphoma 2 (Bcl-2) suggests that MUC16 controls AKT Serine/Threonine Kinase 1 (AKT) regulated apoptotic signaling.…”

Glucose metabolism reprogramming in gynecologic malignant tumors

“…Since tumor metabolism has gradually emerged as a prominent research focus in anticancer therapy, it has been observed that GLUT1 exhibits abnormal expression across various tumor types. In OC, MUC16 and miR-1204 have been found to positively regulate the expression of GLUT1, thereby facilitating enhanced glucose metabolism reprogramming and glycogen synthesis for increased energy production during tumor progression 82 , 106 . This study suggests that GLUT1, serving as an energy indicator, can be utilized to assess the prognostic value for OC patients.…”

MUC1 and MUC16: critical for immune modulation in cancer therapeutics

“…Furthermore, Wang et al. found that MUC16’s regulatory effect on GLUT1 expression might be a contributing factor to the proliferation and progression of ovarian epithelial cancer ( 43 ). In terms of tumor metastasis, Huo et al.…”