Targeting PELP1 Attenuates Angiogenesis and Enhances Chemotherapy Efficiency in Colorectal Cancer

Cancers

Yiran Zhang¹  Hao Zhang¹  Xiaodong Chu¹  Jinghua Pan¹  Yi Yang¹  Yunlong Pan¹  Yabing Yang¹  Jianlin Zhu¹  Zhimeng Yao²  Kai Li²  Yusheng Lin²  Xiao Xiong²  Fan Liu²  Lu Wang² 

[1] Department of General Surgery, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou 510632, China;Institute of Precision Cancer Medicine and Pathology, Jinan University Medical College, Guangzhou 510632, China;

关键词: colorectal cancer;    angiogenesis;    PELP1;    chemotherapy;    tumor vascular normalization;   

DOI  :  10.3390/cancers14020383

来源: DOAJ

【 摘 要 】

Abnormal angiogenesis is one of the important hallmarks of colorectal cancer as well as other solid tumors. Optimally, anti-angiogenesis therapy could restrain malignant angiogenesis to control tumor expansion. PELP1 is as a scaffolding oncogenic protein in a variety of cancer types, but its involvement in angiogenesis is unknown. In this study, PELP1 was found to be abnormally upregulated and highly coincidental with increased MVD in CRC. Further, treatment with conditioned medium (CM) from PELP1 knockdown CRC cells remarkably arrested the function of human umbilical vein endothelial cells (HUVECs) compared to those treated with CM from wildtype cells. Mechanistically, the STAT3/VEGFA axis was found to mediate PELP1-induced angiogenetic phenotypes of HUVECs. Moreover, suppression of PELP1 reduced tumor growth and angiogenesis in vivo accompanied by inactivation of STAT3/VEGFA pathway. Notably, in vivo, PELP1 suppression could enhance the efficacy of chemotherapy, which is caused by the normalization of vessels. Collectively, our findings provide a preclinical proof of concept that targeting PELP1 to decrease STAT3/VEGFA-mediated angiogenesis and improve responses to chemotherapy due to normalization of vessels. Given the newly defined contribution to angiogenesis of PELP1, targeting PELP1 may be a potentially ideal therapeutic strategy for CRC as well as other solid tumors.

【 授权许可】

Unknown