br Conclusion and prospect Small
5. Conclusion and prospect Small GTPases are very important regulatory proteins of eukaryotes. They play crucial regulatory function in various movement processes of organism , , . Different nanoparticles used to investigate the interaction with small GTPases inside VAS2870 have been summarized. At present, related researches only cover a few limited types of nanoparticles and GTPases, the action mechanism of the two still requires a systematic interpretation. Small GTPase family has large family members, but their interaction with nanoparticles is still considered very little. We summarized different nanoparticles mentioned in this review to investigate the interaction with small GTPases inside cells and listed them in Table 1 in nanoparticle structure dependent ways. According to this table, we can more clearly see that inorganic nanoparticles are more widely used in the study of small GTPases than organic polymers. But now there are only 21 examples could be found. One of the key issues in this area is how to dig out and identify small GTPase(s) which is/are related to reveal the involved physiological functions and the interaction with nanoparticles. Analysis on structure and function of small GTPases in virtue of methods of biological chemistry, proteomics, molecular biology and genetics, etc. will contribute to a clear understanding about their molecule action mode. It is expected that the exact action mechanisms will be identified in the future, which will be favorable for the designing of better nanomedicines with higher effectiveness for practical application.
Conflict of interest
Introduction Malignant cancer occurs when rapidly dividing tumor cells acquire the capacity to invade the surrounding tissue. While the primary tumor can often be removed by surgical resection, metastatic cancers are often associated with resistance to chemotherapeutic treatment, have higher post-treatment recurrence rates and are ultimately responsible for the majority of cancer associated mortality (Steeg, 2016). Therefore, there is an urgent therapeutic need for suppression of metastasis. As prerequisite for occurrence of metastasis, carcinoma cells lose their epithelial phenotype and acquire a more motile, mesenchymal phenotype, a process commonly known as epithelial-mesenchymal transition (EMT). EMT allows cells to migrate from their primary site, through the surrounding tissue towards the blood or lymphatic system. The Rho family of small GTPases comprises over 60 members and can be subdivided in multiple subfamilies, based on their structure and function and have a well-recognized role in the regulation of migration by acting on the cytoskeleton. The best characterized subfamilies are the Rho (RhoA, RhoB, RhoC), Rac (Rac1, Rac2, Rac3, RhoG) and Cdc42 (Cdc42, RhoQ, RhoJ) subfamilies. Small GTPases cycle between an inactive GDP-bound and an active GTP-bound bound state. Activation of small GTPases is achieved by guanine nucleotide exchange factors (GEFs) that catalyze the exchange of GDP to GTP (Cherfils & Zeghouf, 2013). Inactivation of small GTPase is achieved by guanine nucleotide activating proteins (GAPs) that stimulate the low intrinsic GTP-hydrolyzing activity of the small GTPases (Fig. 1). The guanine nucleotide dissociation inhibitors (GDIs) interact with the inactive GTPase domains and prevent the dissociation of guanine nucleotides from Rho GTPases (Cherfils & Zeghouf, 2013). Thus, GDIs preserve the inactive GTPase state by preventing GEF-mediated nucleotide exchange, or when they bind to the GTP bound state, they inhibit GTPase activity while maintaining interactions with downstream effectors. Rho proteins interact only in their active GTP-bound state with a range of different effectors and thereby regulate cellular functions. In addition, distinct intracellular localization of Rho proteins with overlapping effectors result in pronounced functional differences.