The Function Of Periostin In Breast Tumor Glycolysis

Breast cancer is the most common malignant tumor in women and one of the three most common malignant tumors in the world.Different therapeutic strategies for distinct molecular types and the implication of some targeted drugs elevate the survival time of patients with breast cancer.However,metastatic breast cancer remains difficult to be cured.Previous studies have shown that periostin(POSTN)can promote the development of breast cancer by affecting cancer stem cells and tumor microenvironments,but it is not clear whether POSTN affects breast tumor metabolism.In this study,we used MMTV-PyMT,a mouse model of spontaneous breast cancer,to determine the relationship between POSTN and tumor metabolism.We discovered a glycolytic decrease in breast tumor after Po.stn knockout by 18F-FDG-PET-CT and lactate assays.We further isolated the tumor cells from the mice with spontaneous breast tumors and found that the Postn-/-cells also have reduced glycolysis.After detecting glycolytic-related enzymes at the tumor tissue and cellular levels,we found that Postn knockdown reduces hexokinase 2(HK2)in tumor cells,which may be the main reason for the decrease of glycolysis levels.We then demonstrate that POSTN promotes HK2 via FAK but not via Akt.We further demonstrate that Postn knockout decreases the protein level and nuclear input of HIF1?,suggesting that the change of HIF1? may influence HK2.We further found that HK2 expression is decreased in the lung metastases of Postn-knockout mice with spontaneous breast tumors,indicating that Postn knockout also affects the metabolism of lung metastases.Finally,we found a positive correlation between POSTN and HK2 expression in human breast cancer samples that are HER2-negative and hormone-positive.This study is the first one to investigate the function of POSTN in tumor metabolism and identify a relationship between POSTN and HK2 in breast tumor metabolism.It will help us to better understand the metabolic function of POSTN in tumors and to develop targeted drugs for breast cancer.