RGS (regulator of G protein signaling) proteins serve as negative regulators of G protein signaling. Since the discovery of the first RGS protein, more than 37 RGS members encoded by the human genome have been identified. According to their RGS domain homology and common functional domain architecture, RGS members are divided into eight subfamilies and recent studies indicate that they may play multi-tasking roles in cellular regulation.

Although RGS20 is highly expressed in metastatic melanomas than in primary melanomas, the role of RGS20 on tumorigenesis and metastasis remains unclear. To explore these functions of RGS20, a constitutively active mutant of H-Ras (H-RasGV) was stably expressed with or without RGS20 in NIH3T3 cells. Conversely, RGS20 was stably knocked down in A...[ Read more ]

RGS (regulator of G protein signaling) proteins serve as negative regulators of G protein signaling. Since the discovery of the first RGS protein, more than 37 RGS members encoded by the human genome have been identified. According to their RGS domain homology and common functional domain architecture, RGS members are divided into eight subfamilies and recent studies indicate that they may play multi-tasking roles in cellular regulation.

Although RGS20 is highly expressed in metastatic melanomas than in primary melanomas, the role of RGS20 on tumorigenesis and metastasis remains unclear. To explore these functions of RGS20, a constitutively active mutant of H-Ras (H-RasGV) was stably expressed with or without RGS20 in NIH3T3 cells. Conversely, RGS20 was stably knocked down in A549 human small lung cancer cell. Using these cellular models, it was shown that NIH3T3 fibroblasts lost contact inhibition upon expressing oncogenic Ras in adherent cultures. RGS20 enhanced cell aggregation in NIH3T3 fibroblasts expressing oncogenic Ras. Compared with RGS20, RGS19 (which also belongs to the RZ subfamily) showed no significant effect on cell aggregation in NIH3T3 fibroblasts. Cells lacking contact inhibition would consequently grow into spheres which might reflect initial outgrowth of tumors. Additionally, in vitro experiments showed that the knockdown of RGS20 reduced the migration and invasion ability of A549 cells without influencing their proliferation rate.

These observations supported the hypothesis that RGS20 might have a role in potentiating tumor metastasis by enhancing cell aggregation and migration. Further investigation of the mechanisms or signaling pathways involved in these effects are required. These findings support the notion that RGS proteins might serve additional functions other than being GTPase accelerating proteins.