Translational and Molecular Biology Laboratory (TMBL), St. John's Research Institute (SJRI), Bangalore, 560034, India.
School of Integrative Health Sciences, The University of Trans-Disciplinary Health Sciences and Technology (TDU), Bangalore, 560064, India.
J Exp Clin Cancer Res. 2019 Jul 24;38(1):328. doi: 10.1186/s13046-019-1327-4.
Tumor heterogeneity results in differential response to therapy due to the existence of plastic tumor cells, called cancer stem cells (CSCs), which exhibit the property of resistance to therapy, invasion and metastasis. These cells have a distinct, signaling network active at every stage of progression. It is difficult to envisage that the CSCs will have a unique set of signaling pathways regulating every stage of disease progression. Rather, it would be easier to believe that a single pivotal pathway having significant contribution at every stage, which can further turn on a battery of signaling mechanisms specific to that stage, would be instrumental in regulating the signaling network, enabling easy transition from one state to another. In this context, we discuss the role of RhoC which has contributed to several phenotypes during tumor progression.RhoC (Ras homolog gene family member C) has been widely reported to regulate actin organization. It has been shown to impact the motility of cancer cells, resultantly affecting invasion and metastasis, and has contributed to carcinoma progression of the breast, pancreas, lung, ovaries and cervix, among several others. The most interesting finding has been its indispensable role in metastasis. Also, it has the ability to modulate various other phenotypes like angiogenesis, motility, invasion, metastasis, and anoikis resistance. These observations suggest that RhoC imparts the plasticity required by tumor cells to exhibit such diverse functions based on microenvironmental cues. This was further confirmed by recent reports which show that it regulates cancer stem cells in breast, ovary and head and neck cancers. Studies also suggest that the inhibition of RhoC results in abolition of advanced tumor phenotypes.Our review throws light on how RhoC, which is capable of modulating various phenotypes may be the apt core signaling candidate regulating disease progression. Additionally, mice studies show that RhoC is not essential for embryogenesis, giving scope for its development as a possible therapeutic target. This review thus stresses on the need to understand the protein and its functioning in greater detail to enable its development as a stem cell marker and a possible therapeutic target.
肿瘤异质性导致对治疗的反应不同，这是由于存在可塑性肿瘤细胞，称为癌症干细胞 (CSC)，它们表现出对治疗、侵袭和转移的抵抗力。这些细胞具有独特的信号网络，在进展的每个阶段都活跃。很难想象 CSC 会有一组独特的信号通路来调节疾病进展的每个阶段。相反，人们更容易相信，在每个阶段都有一个重要的关键途径，它可以进一步开启与该阶段特异性相关的一系列信号机制，这将有助于调节信号网络，使细胞能够轻松地从一个状态过渡到另一个状态。在这种情况下，我们讨论了 RhoC 在肿瘤进展过程中所起的作用。
RhoC（Ras 同源基因家族成员 C）已被广泛报道可调节肌动蛋白组织。它已被证明会影响癌细胞的运动能力，从而影响侵袭和转移，并有助于乳腺癌、胰腺癌、肺癌、卵巢癌和宫颈癌等几种癌症的进展。最有趣的发现是其在转移中的不可或缺作用。此外，它还具有调节其他多种表型的能力，如血管生成、运动性、侵袭性、转移性和抗凋亡性。这些观察结果表明，RhoC 赋予肿瘤细胞所需的可塑性，使其根据微环境线索表现出如此多样化的功能。最近的研究报告进一步证实了这一点，这些报告表明它调节乳腺癌、卵巢癌和头颈部癌症中的癌症干细胞。研究还表明，抑制 RhoC 会导致高级肿瘤表型的消除。
我们的综述阐明了 RhoC 如何能够调节各种表型，它可能是调节疾病进展的合适核心信号候选物。此外，小鼠研究表明 RhoC 对于胚胎发生不是必需的，这为其作为可能的治疗靶点的发展提供了空间。因此，本综述强调需要更详细地了解该蛋白及其功能，以便将其开发为干细胞标志物和可能的治疗靶点。
