Cancer cells can remodel surrounding microenvironments to facilitate cell growth, invasion, and migration by secreting proteins that educate surrounding stromal cells. We report that p85^S6K1, the longest isoform of S6K (ribosomal protein S6 kinase), but not the shorter isoform p70^S6K1 or p56^S6K2, was secreted from cancer cells through its HIV TAT-like, N-terminal six-arginine motif. The exogenously produced p85^S6K1 protein entered cultured transformed and nontransformed cells to promote or confer malignant behaviors, leading to increased cell growth and migration. When injected into mice, the p85^S6K1 protein enhanced the growth of xenografted breast cancer cells and lung metastasis. Hence, our findings reveal a role for p85^S6K1 as a secreted oncogenic kinase and provide a mechanism by which cancer cells remodel their microenvironment by transforming the surrounding cells to drive tumorigenesis.

癌细胞可以通过分泌教育周围基质细胞的蛋白质来重塑周围的微环境，从而促进细胞的生长，侵袭和迁移。我们报告说，p85 ^S6K1是S6K的最长同工型（核糖体蛋白S6激酶），而不是较短的同工型p70 ^S6K1或^{p56 S6K2}，是通过其HIV TAT样，N端六精氨酸基序从癌细胞中分泌的。外源产生的p85 ^S6K1蛋白进入培养的转化和未转化细胞，以促进或赋予恶性行为，从而导致细胞生长和迁移增加。当将p85 ^S6K1注入小鼠体内时蛋白增强异种移植乳腺癌细胞的生长和肺转移。因此，我们的发现揭示了p85 ^S6K1作为一种分泌的致癌激酶的作用，并提供了一种机制，癌细胞通过转化周围的细胞来驱动肿瘤发生，从而重塑其微环境。