SGK3 (CISK) may induce tumor angiogenesis (Hypothesis)

Abstract

Abstract. Serum-and glucocorticoid-inducible protein kinase 3 (SGK3), also known as cytokine-independent survival kinase (CISK), encoded by chromosome 8q12.2, is a downstream mediator of phosphatidylinositol 3-kinase (PI3K) oncogenic signaling. As a downstream target of PI3K, SGK3 has been reported to mediate pivotal roles in oncogenic progress in various cancers, including breast cancer, ovarian cancer and hepatocellular carcinoma. Functionally parallel to v-akt murine thymoma viral oncogene homolog (AKT)/protein kinase B, SGK3 serves as a hallmark mediating glycogen synthase kinase-β (GSK3-β), B-cell lymphoma (Bcl)-2-associated death promoter, forkead family of transcription factors, Bcl-extra large, Bcl-2, mammalian target of rapamycin, C-X-C chemokine receptor type 4 (CXCR4) and numerous other molecules in cell proliferation, growth, survival, migration and even tumor angiogenesis. Tumor angiogenesis is recognized as an essential step for tumor growth, invasion and metastasis, and it has become an intriguing target for anticancer drug development for tumor investigators worldwide. An abundance of experiments have been performed to investigate the role of the phosphoinositide 3-kinase (PI3K)/AKT pathway in regulating tumor angiogenesis. The mechanism of angiogenesis regulated by the PI3K/AKT pathway is, to a certain extent, clear. Although a number of SGK3 target molecules, including CXCR4 and GSK3β, have demonstrated potential roles in promoting angiogenesis, the exact association between angiogenesis and SGK3 remains unclear. Thus, we hypothesize that SGK3, parallel to AKT, may also be important in mediating angiogenesis. Identifying the role of SGK3 in tumor angiogenesis will certainly present a novel perspective on the malignant transformation of tumors, as well as a target for tumor therapy.

MicroRNA-144-3p suppresses tumor growth and angiogenesis by targeting SGK3 in hepatocellular carcinoma

“…Encoded by chromosome 8q12.2, SGK is known as a downstream mediator of phosphatidylinositol 3-kinase (PI3K) oncogenic signaling. It has also been proved that SGK3 plays a pivotal role in oncogenic progress in various cancers, including breast cancer, ovarian cancer and hepatocellular carcinoma ( 27 ). In physiological research aspect, some studies reported that SGK1 is necessary for vascular remodeling during angiogenesis ( 28 ), and ablation of SGK1 impairs endothelial cell migration and tube formation leading to decreased neo-angiogenesis following myocardial infarction ( 29 ).…”

FK506 binding protein 5 regulates cell quiescence-proliferation decision in zebrafish epithelium

“…SGK1 increases the protein abundance and/or activity of several ion channels, solute carriers, and Na+/K+-ATPases (Lang and Shumilina 2013). Overexpression of SGK3 in hepatocellular carcinoma has been shown to increase cell cycle progression through G1 by inactivating glycogen synthase kinase-β (GSK3-β) and stabilizing CCND1 (Hou, Lai et al 2015). Future genetic studies are needed to elucidate the possible roles of Sgk1 and/or Sgk3 in NaR cell quiescence-proliferation regulation.…”

FK506‐binding protein 5 regulates cell quiescence‐proliferation decision in zebrafish epithelium

“…SGK1 increases the protein abundance and/or activity of several ion channels, solute carriers and Na + /K + ‐ATPases [32]. Overexpression of SGK3 in hepatocellular carcinoma has been shown to increase cell cycle progression through G1 by inactivating glycogen synthase kinase‐β and stabilising CCND1 [33]. Future genetic studies are needed to elucidate the possible roles of Sgk1 and/or Sgk3 in NaR cell quiescence‐proliferation regulation.…”