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.

中文翻译：

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SEC23A 通过分泌 PF4 与 SPARC 合作抑制 MAPK 信号通路抑制黑色素瘤转移

黑色素瘤向远处器官的转移是一个多步骤的过程，其中肿瘤微环境（TME）可能发挥重要作用。然而，转移进展与 TME 之间的关系是错综复杂的。在本研究中，利用转移定植能力不同的黑色素瘤衍生细胞系OL（寡转移）和POL（多转移），我们阐明了一种涉及“SEC23A-PF4-MAPK/ERK轴”的新机制，其中PF4由COPII转运。通过抑制 MAPK/ERK 信号通路阻碍转移。此外，SPARC 可以协同作用以增强 Pf4 对 ERK 磷酸化和黑色素瘤细胞转移的抑制作用。我们的研究结果表明靶向癌细胞分泌组进行治疗开发的可能性。