These data indicate that AKT1 kinase, which is frequently activated in human cancer, is a determinant in oncogenesis and a potential target for cancer intervention.
The anti-apoptotic proto-oncogene, AKT, has been implicated in the molecular pathogenesis of a variety of human malignancies; however, no data exist on the role of AKT in colon carcinogenesis.
In this review, we will summarize the signaling properties and highlight the specificities of AKT kinases that have emerged from the study of human cancer and animal models.
Several reports implicated AKT in the molecular pathogenesis of different human malignancies and overexpression of AKT was recently demonstrated to be an early event in colorectal carcinogenesis.
Our findings highlight the important role of cAMP signaling in DLBCL and suggest that clinically relevant PDE4 and PI3K/AKT inhibitors might be useful in the treatment of DLBCL and additional B-lymphoid malignancies with increased PDE4B expression.
We also review various pathogenic mechanisms contributing to activation of the AKT pathway in human malignancy as well as current pharmacologic strategies to target therapeutically components of this pathway.
The role of the IGF system in cancer should be examined in the context of the extra-cellular and intra-cellular signalling networks, in particular: phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt/PKB), mammalian target of rapamycin (mTOR), and forkhead transcription factors (FOXO).
As a well-established negative effector in the phosphatidylinositol 3-kinase/AKT signaling pathway, FOXO1A inactivation in cancer would impair the therapeutic effect of phosphatidylinositol 3-kinase/AKT inhibitors in cancer treatment.
Many tumors and tumor cells display elevated Akt protein expression and activity, and many of the proteins which regulate Akt itself are also often mutated in cancer.
This mechanism indicates a direct role of AKT1 in human cancer, and adds to the known genetic alterations that promote oncogenesis through the phosphatidylinositol-3-OH kinase/AKT pathway.
The phosphoinositide 3-kinase (PI3K)/AKT pathway has been shown to be central in the promotion of cell survival since the alteration of this signalling cascade is a frequent event in human malignancies.
Given the well-defined roles of CD44, phosphorylated AKT in apoptosis and cancer, these results indicate that CD44-induced cell migration is dependent on its complex formation with Lyn and its consequent regulation of AKT phosphorylation and cofilin expression.
We investigated ERK and AKT phosphorylation in normal (PNT1A) and cancer (PC-3) prostate cells after adhesion to ECM and the effects upon BRCA2 and cell proliferation.