Despite continuous exertion made, colon cancer still represents a major health problem and its incidence continues being high worldwide. There is growing evidence in support of the cancer stem cells (CSCs) being central in the initiation of this cancer, and CSCs have been the focus of various studies for the identification of new ways of treatment. Lately, the proprotein convertases (PCs) were reported to regulate the maturation and expression of various molecules involved in the malignant phenotype of colon cancer cells, however, the identity of the molecules regulated by these serine proteases in CSCs is unknown. In this study, we used the general PCs inhibitor, the Decanoyl-RVKR-chloromethylketone (Decanoyl-RVKR-CMK) that inhibits all the PCs found in the secretory pathway, and analyzed its effect on CSCs using RNA-seq analysis. Remarkably, from the only 9 up-regulated genes in the human SW620-derived sphere-forming cells, we identified 7 of the 11 human metallothioneins, all of them localized on chromosome 16, and zinc related proteins as downstream effectors of the PCs. The importance of these molecules in the regulation of cell proliferation, differentiation and chemoresistance, and their reported potential tumor suppressor role and loss in colon cancer patients associated with worse prognosis, suggests that targeting PCs in the control of the malignant phenotype of CSCs is a new potential therapeutic strategy in colon cancer.

尽管不断地努力，但结肠癌仍然是一个主要的健康问题，在世界范围内其发病率仍然很高。越来越多的证据支持癌干细胞（CSCs）在该癌症的发生中起关键作用，并且CSCs已成为各种研究的重点，用于鉴定新的治疗方法。最近，据报道前蛋白转化酶（PCs）调节结肠癌细胞恶性表型中涉及的各种分子的成熟和表达，但是，在CSC中由这些丝氨酸蛋白酶调节的分子的身份尚不清楚。在这项研究中，我们使用了通用的PC抑制剂Decanoyl-RVKR-氯甲基酮（Decanoyl-RVKR-CMK）来抑制分泌途径中发现的所有PC，并使用RNA-seq分析法分析了其对CSC的作用。值得注意的是 从人类SW620来源的成球细胞中仅有的9个上调基因中，我们鉴定了11种人类金属硫蛋白中的7种（均位于16号染色体上）和锌相关蛋白作为PC的下游效应子。这些分子在调节细胞增殖，分化和化学抗性中的重要性，以及它们在与预后较差相关的结肠癌患者中潜在的抑癌作用和丧失的报道，表明靶向PC来控制CSC的恶性表型是一种新的方法结肠癌的潜在治疗策略。