Satelli Arun, Hu Jiemiao, Xia Xueqing, Li Shulin
Department of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Department of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, Texas;; The University of Texas Graduate School of Biomedical Sciences, Houston, Texas.
J Cancer. 2016 Aug 12;7(13):1824-1832. doi: 10.7150/jca.15622. eCollection 2016.
Cancer cell signaling, growth, morphology, proliferation and tumorigenic potential are largely depending on the signaling molecules present naturally in the tumor microenvironment and the identification of key molecules that drive the tumor progression is critical for the development of new modalities for the prevention of tumor progression. High concentrations of vimentin in the blood of cancer patients have been reported, however the function of blood circulating vimentin remains unknown. Here, we investigated the functional role of exogenously supplemented vimentin on colon cancer cells and examined the Wnt Signaling activation and cancer cell invasion. Vimentin when supplemented to the cancer cells remained bound to the surface of the cancer cells. Furthermore, bound vimentin activates Wnt signaling pathway as detectable by increased β-catenin accumulation in the nucleus with concomitant activation of β-catenin-dependent transcription of Wnt signaling downstream targets. Functionally, there was an increase in the rate of cellular invasion in these cancer cells upon binding with vimentin. Our results thus suggest that free vimentin in the tumor microenvironment acts as a positive regulator of the β-catenin signaling pathway, thus providing a basis for cancer invasive properties.
癌细胞的信号传导、生长、形态、增殖和致瘤潜力在很大程度上取决于肿瘤微环境中天然存在的信号分子，识别驱动肿瘤进展的关键分子对于开发预防肿瘤进展的新方法至关重要。已有报道称癌症患者血液中波形蛋白浓度较高，但循环血液中波形蛋白的功能仍不清楚。在此，我们研究了外源性补充波形蛋白对结肠癌细胞的功能作用，并检测了Wnt信号激活和癌细胞侵袭情况。当向癌细胞补充波形蛋白时，它会与癌细胞表面结合。此外，结合的波形蛋白可激活Wnt信号通路，表现为细胞核中β-连环蛋白积累增加，同时Wnt信号下游靶标的β-连环蛋白依赖性转录被激活。在功能上，这些癌细胞与波形蛋白结合后细胞侵袭率增加。因此，我们的结果表明肿瘤微环境中的游离波形蛋白作为β-连环蛋白信号通路的正向调节因子，从而为癌症的侵袭特性提供了基础。
