2014年8月27日讯 ，一项新的科学研究已确定了姜黄素（来源于香料姜黄的生物活性分子），预防结肠癌癌细胞转移的机制之一。研究发现，姜黄素能阻断结肠癌蛋白质--皮层蛋白。皮层蛋白对于癌细胞运动是必需的蛋白质，它经常在癌症中过度表达，从而促使癌细胞转移到身体其他器官。
在美国，结肠癌是癌症相关死亡的第二大原因，是男性和女性第三大常见癌症。当肿瘤转移至其他器官，病人的存活机会大大减少。因此，寻找新的方式来防止癌细胞转移仍然是迫切需要的。
姜黄素是姜黄的活性成分，已被科学研究用于许多类型癌症的治疗。姜黄素已被证明具有癌化学预防作用，能扭转，抑制或阻止癌症发展的能力。新的研究发现了姜黄素阻止结肠癌细胞转移的机制之一。研究小组发现，皮层蛋白的活化部分pTyr421在结肠恶性肿瘤中是过度激活的。我们发现，皮层蛋白过度激活是由于过度磷酸化过程引发的。
磷酸化负责开启和关闭蛋白质，改变蛋白质的功能和活性。皮层蛋白过度磷酸化活化已与癌症侵略性密切相关。研究人员用姜黄素处理结肠癌细胞发现，姜黄素能关闭皮层蛋白的活性形式，因此，当皮层蛋白被关闭时，癌细胞失去移动能力，并且不能转移到身体的其他部分。”
更具体地说，姜黄素通过与皮层蛋白相互作用，并激活PTPN1酶，“关闭”皮层蛋白。PTPN1酶作为一种磷酸酶，可从皮层蛋白中去除磷酸基团，也即“去磷酸化”过程。而皮层蛋白去磷酸化与结肠癌细胞迁移能力降低相关。
通过确定姜黄素激活酶PTPN1，然后关闭皮层蛋白的活性部位pTyr421，我们认为其可以开发成针对癌细胞皮层蛋白的化学预防药物，以防止癌症的转移性。
doi:10.1371/journal.pone.0085796
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pTyr421 Cortactin Is Overexpressed in Colon Cancer and Is Dephosphorylated by Curcumin: Involvement of Non-Receptor Type 1 Protein Tyrosine Phosphatase (PTPN1)
Vijayababu M. Radhakrishnan,et al.
Cortactin (CTTN), first identified as a major substrate of the Src tyrosine kinase, actively participates in branching F-actin assembly and in cell motility and invasion. CTTN gene is amplified and its protein is overexpressed in several types of cancer. The phosphorylated form of cortactin (pTyr421) is required for cancer cell motility and invasion. In this study, we demonstrate that a majority of the tested primary colorectal tumor specimens show greatly enhanced expression of pTyr421-CTTN, but no change at the mRNA level as compared to healthy subjects, thus suggesting post-translational activation rather than gene amplification in these tumors. Curcumin (diferulolylmethane), a natural compound with promising chemopreventive and chemosensitizing effects, reduced the indirect association of cortactin with the plasma membrane protein fraction in colon adenocarcinoma cells as measured by surface biotinylation, mass spectrometry, and Western blotting. Curcumin significantly decreased the pTyr421-CTTN in HCT116 cells and SW480 cells, but was ineffective in HT-29 cells. Curcumin physically interacted with PTPN1 tyrosine phosphatases to increase its activity and lead to dephosphorylation of pTyr421-CTTN. PTPN1 inhibition eliminated the effects of curcumin on pTyr421-CTTN. Transduction with adenovirally-encoded CTTN increased migration of HCT116, SW480, and HT-29. Curcumin decreased migration of HCT116 and SW480 cells which highly express PTPN1, but not of HT-29 cells with significantly reduced endogenous expression of PTPN1. Curcumin significantly reduced the physical interaction of CTTN and pTyr421-CTTN with p120 catenin (CTNND1). Collectively, these data suggest that curcumin is an activator of PTPN1 and can reduce cell motility in colon cancer via dephosphorylation of pTyr421-CTTN which could be exploited for novel therapeutic approaches in colon cancer therapy based on tumor pTyr421-CTTN expression.
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