SEC23A Inhibit Melanoma Metastatic through Secretory PF4 Cooperation with SPARC to Inhibit MAPK Signaling Pathway
Bin Zeng, Zhiwei Sun, Qiting Zhao, Doudou Liu, Hao Chen, Xiaoshuang Li, Hongyun Xing, Jianyu Wang
Abstract
Metastasis of melanoma to the distant organs is a multistep process in which the tumor microenvironment (TME) may play an important role. However, the relationship between metastatic progression and TME is intricate. In the present study, using melanoma derivative cell lines OL (oligometastatic) and POL (polymetastatic) that differ in their metastatic colonization capability, we have elucidated a new mechanism involving "SEC23A-PF4-MAPK/ERK axis" in which PF4 transported by COPII hinders metastasis through inhibition of MAPK/ERK signaling pathway. Furthermore, SPARC can act cooperatively to enhance the inhibition of Pf4 on ERK phosphorylation and melanoma cell metastasis. Our findings show the possibility of targeting cancer cell secretome for therapeutic development.