Estrogen activated the AKT pathway in BRCA1-deficient tumor cells independent of ER, and pharmaceutical inhibition of AKT activity suppressed EMT and cell proliferation preventing BRCA1 deficient tumor progression.
This review discusses the role of PRAS40 and possible feedback mechanisms, and alterations in AKT/PRAS40/mTOR signaling that have been implicated in the pathogenesis of tumor progression.
TIS21<sup>/BTG2</sup> significantly lost in the infiltrating ductal carcinoma, but it can inhibit cancer growth via the TIS21<sup>/BTG2</sup>-tsc1/2-mTORc1-p70S6K axis and downregulate cancer progression via the TIS21<sup>/BTG2</sup>-mTORc2-AKT1-NFAT1-PHLPP2 pathway.
These observations indicate that Smad4/Pten-mutant mice mimic the tumor progression of human pancreatic cancers that are driven by activation of the AKT-mTOR pathway, and uncovered a synergistic action of Smad4 and Pten in repressing pancreatic tumorigenesis.
Mechanistically, high levels of TRIM44 increased the levels of p-AKT (T308) and p-mTOR (S2448), and a specific AKT inhibitor inhibited TRIM44-induced tumor progression.
These studies elucidate a new layer of regulation in the PI3K/AKT/mTOR pathway with relevance to mammary development and tumour progression and identify miR-184 as a putative breast tumour suppressor.
These results prompted us to investigate the factors affecting the tumorigenicity of <i>MAEL</i> Further experimentation demonstrated that <i>MAEL</i> enhanced the expression of phosphorylated Akt1, with subsequent phosphorylation of nuclear factor kappa B (NF-κB) subunit RelA in tumor cells, and chemoattracted myeloid-derived suppressor cells (MDSCs) by upregulating interleukin-8 (IL8) to accelerate tumor progression in the tumor microenvironment.
HIF-1 is also activated in cancer cells by tumor suppressor (e.g., VHL) loss of function and oncogene gain of function (leading to PI3K/AKT/mTOR activity) and mediates metabolic alterations that drive cancer progression and resistance to therapy.
In addition, consistent with the human cancer, AKT-mTOR-p70(S6K) signaling and vascular growth factor and its receptor were activated to facilitate tumor progression.
We have previously demonstrated an increased expression of gastrin-releasing peptide (GRP) and its receptor, GRPR, in neuroblastoma and that GRP activates the PI3K-AKT pathway as a proangiogenic factor during tumor progression.
Endostar, a novel safe and well-tolerated recombinant human endostatin, can suppress the expression of VEGF and the activation of ERK, MAPK, and AKT, and then inhibit tumor progression.
AKT/mTOR status was inactivated in pre-imatinib and on-treatment samples in eight patients with effective imatinib; however, the status of six patients was changed from inactivated to activated in 12 patients at the time of tumor progression.
Cytogenetic studies and mouse models are beginning to identify genes and signalling pathways that have roles in tumour progression, such as hedgehog, p53, insulin-like growth factor, cyclin-dependent kinase 4, hypoxia-inducible factor, matrix metalloproteinases, SRC and AKT, suggesting potential new therapeutic approaches.
We showed that suppression of GRM1 expression in several human melanoma cell lines resulted in a reduction in the number of viable cells and a decrease in stimulated mitogen-activated protein kinase (MAPK) and PI3K/AKT and suppressed tumor progression in vivo.
While the PI3K/AKT pathway has been investigated as a co-therapeutic target with ARPI for advanced PCa, whether this strategy can prevent tumor progression to t-NEPC remains unknown.
The tumour microenvironment has an important role in cancer progression and recent reports have proposed that stromal AKT is activated and regulates tumourigenesis and invasion.
Accordingly, we reported a resistance mechanism to androgen deprivation therapy (ADT) mediated by miR-135a which might be downregulated by androgen depletion and/or PI3K/AKT hyperactivation, in castration-resistant prostate cancer (CRPC), thus promoting tumor progression.
Frequent mutations and gene expression alterations in the PI3K/AKT and mitogen-activated protein kinase-ERK pathways lead to deregulated cell growth and the acquisition of invasive properties, which facilitates tumour progression and confers resistance to chemotherapy.