The protein expression of PTEN, PI3K and AKT was detected by western blotting; relationships between the expression level of PTEN mRNA and the clinical features of RCC were analyzed.
Our results suggested that SGK2 promoted RCC progression by mediating the phosphorylation of extracellular regulated protein kinases (ERK) 1/2 and Protein kinase B (AKT/PKB), indicating that SGK2 might serve as a potential prognostic marker and therapeutic target for renal cancer patients.
These findings demonstrate that atopic expression of Tescalcin facilitates the survival, migration and invasion of RCC cells via NHE1/pHi axis as well as AKT/ NF-κB signaling pathway, providing new perspectives for the future study of Tescalcin as a therapeutic target for RCC.
In this article, we briefly review current evidence regarding mechanisms of resistance in RCC and treatment strategies to overcome resistance with a special focus on the PI3K/AKT/mTOR pathway.
Interruption of PI3K→︀AKT→︀GSK3β→︀AM signaling via specific inhibitors led to decreased recruitment of mast cells, and targeting this infiltrating mast cell-related signaling via an AKT-specific inhibitor suppressed RCC angiogenesis in xenograft mouse models.
Together, our results reveal a new mechanism that macrophages in the RCC tumor microenvironment could increase RCC metastasis via activation of the AKT/mTOR signals.
To further investigate the reason for the low expression of hepaCAM in renal carcinoma and the corresponding molecular mechanisms, we detected renal carcinoma OS-RC-2 cell lines containing high expression of hepaCAM; and hepaCAM and p-AKT were also detected in these cells.
Together, our study reveals a novel mechanism of PI3K-AKT inhibition-mediated feedback regulation and may identify FoxO as a novel biomarker to stratify patients with RCC for PI3K or AKT inhibitor treatment, or a novel therapeutic target to synergize with PI3K-AKT inhibition in RCC treatment.
Intriguingly, RCC precursor cells where Jade-1 was silenced exhibited an increased capacity for AKT-dependent anchorage-independent growth, in support of a tumor suppressor function for Jade-1 in RCC.
This study proposes a novel treatment paradigm where combining PI3K/AKT/mTOR pathway inhibitors and autophagy inhibitors lead to enhanced RCC cell apoptosis.