Our findings indicate that the adverse prognosis associated with TP53 and PIK3CA mutations in human cancers can be functionally replicated in mouse models of type I→type II OvCA progression.
Likewise, the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway is also a central regulator of the ovarian cancer.
We used six whole-exome-sequenced primary HGSOC/USC cell-lines and three xenografts overexpressing HER2/neu and harboring mutated or wild-type PIK3CA/PIK3R1 genes to evaluate the role of PI3K-mutations as potential mechanism of resistance to afatinib, an FDA-approved pan-c-erb-inhibitor in clinical trials in USC.
Our results indicate that FAK inhibition can suppress ovarian cancer cells migration and invasion through inhibiting downstream signaling (PI3K/AKT), which might be a therapeutic target or biomarker for ovarian cancer.
The current results highlight the role of miR‑381‑mediated regulation of PIK3CA in the development and progression of ovarian cancer and suggest that restoration of miR‑381 to normal levels in ovarian cancer cells may constitute a therapeutic strategy for patients.
Recently, it has been reported that somatic mutations within the PI3K catalytic subunit, PIK3CA, are common (25-40%) among colorectal, gastric, breast, ovarian cancers, and high-grade brain tumors.
High prevalence of genetic alterations in PI3K/AKT pathway in a Middle Eastern ovarian carcinoma provides genetic evidence supporting the notion that dysregulated PI3K/AKT pathways play an important role in the pathogenesis of ovarian cancers.
Here, we show that dual inhibition of PI3K/mTOR in ovarian cancer-spheroids leads to death of inner matrix-deprived cells, whereas matrix-attached cells are resistant.
Activation of the phosphatidylinositol 3' kinase (PI3K) pathway occurs in a significant fraction of both types of ovarian cancer, driven predominantly by mutations in type I and amplification in type II.
Cisplatin-induced CCL5 secretion from CAFs promotes cisplatin-resistance in ovarian cancer via regulation of the STAT3 and PI3K/Akt signaling pathways.
One patient exhibited mutations both in PIK3CA and PTEN at discordant sites between endometrial and ovarian carcinomas, whereas the other 4 exhibited concordant mutations.
These data demonstrate that different repertoires of downstream signaling proteins, particularly those of the MEK6-p38 MAPK-CK2 pathway and the PI3K pathway, are correlated with phenotypic manifestations of a cell culture model of OSE at progressive stages in the development of ovarian cancer.
The USP13 gene is co-amplified with PIK3CA in 29.3% of high-grade serous ovarian cancers and its overexpression is significantly associated with poor clinical outcome.
These data suggested that PI3K induced epithelial-to-mesenchymal transition and promoted cell migration and invasion by activating the PI3K/AKT pathway in ovarian cancer.
The gene of phosphatidylinositol 3-kinase catalytic subunit alpha (PIK3CA) has been implicated as an oncogene in ovarian cancer [L. Shayesteh et al., Nat.Genet., 21: 99-102, 1999].