A detailed molecular genetic analysis of the primary and metastatic tumors demonstrated somatic mutations in 2 well-known cancer genes associated with regulation of PI3K/AKT signaling pathway: (1) PIK3CA, which encodes the catalytic alpha subunit of the phosphoinositide-3-kinase, and (2) PTEN, which encodes phosphatase and tensin homolog.
In this review, we describe PI3K family members and their functions, especially the subunits of class I PI3K, their alterations in cancers, as well as PI3K inhibitors and their clinical trial status in cancer-targeted therapy.
Here we discuss our current understanding of the molecular events controlling cellular metabolism downstream of PI3K and AKT and of how these events couple two major hallmarks of cancer: growth factor independence through oncogenic signalling and metabolic reprogramming to support cell survival and proliferation.
The Ras/Raf/MAPK and PI3K/Akt/mTOR pathways are key signaling cascades involved in the regulation of cell proliferation and survival, and have been implicated in the pathogenesis of several types of cancers, including acute myeloid leukemia (AML).
Chronic <i>Helicobacter pylori</i> infection increases the risk of gastric cancer and induction of hypoxia-induced factor (HIF), which is frequently associated with the development and progression of several types of cancer.We recently showed that <i>H. pylori</i> activation of the PI3K-AKT-mTOR pathway in gastric cells increased HIF-1α expression.Here, we identified the <i>H. pylori</i> virulence factor responsible for HIF-1α induction.A mutant of the <i>H. pylori</i> 84-183 strain was identified with reduced ability to induce HIF-1α.
Inactivation of the transcription factor and tumor suppressor p53, and overexpression or mutational activation of PIK3CA, which encodes the p110alpha catalytic subunit of phosphatidylinositol-3-kinase (PI3K), are two of the most common deleterious genomic changes in cancer, including in ovarian carcinomas.
The results affirm the utility of systematic characterization of the cancer genome in clinically annotated specimens and suggest the particular importance of the PI3K pathway in patients who have aggressive endometrial cancer.
PIK3CA, AKT1, and PTEN are the fundamental molecules of the PI3K/AKT pathway with increased mutation rates in cancer cases leading to aberrant regulation of the pathway.
These findings revealed a novel mechanism by which 14-3-3ζ overexpression activates PI3K, a key node in the mitogenic signaling network known to promote malignancies in many cell types.
Cyclooxygenase-2 (COX-2) and phosphatidylinositol 3-kinase (PI3K)/Akt play a critical role in the formation of many malignant tumors, and have been shown to be important therapeutic targets.
Mitogen-activated protein kinase (MAPK) cascade and phosphatidylinositol 3-kinase (PI3K) survival pathways are frequently activated in the progression of gastrointestinal malignancies.
These studies extend our understanding of the architecture of PI3Ks and provide insight into how two classes of mutations that cause a gain in function can lead to cancer.
Using small molecule inhibitors of NF-κB, STAT-3 and PI3K and by overexpression of PI3K, we provide evidence to show that AXT inhibits NF-κB and STAT-3 signalling and cancer hallmarks by restraining the kinase activity of PI3K/Akt.
The Cancer Genome Atlas integrative analysis of GBM reported the striking finding of genetic alterations in the p53 and PI3K pathways in more than 80% of GBMs.