SGK3 (CISK) may induce tumor angiogenesis (Hypothesis).

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.