Low PTEN expression and overexpression of phosphorylated Akt&lt;sup&gt;Ser473&lt;/sup&gt; and Akt&lt;sup&gt;Thr308&lt;/sup&gt; are associated with poor overall survival in upper tract urothelial carcinoma

Weng, Wen‐Hui; Yu, Kai-Jie; Li, Liang-Chen; Pang, Yeu-Jye; Chen, Ying-Tzu; Pang, See‐Tong; Chuang, Cheng-Keng

doi:10.3892/ol.2020.12210

Cited by 3 publications

(1 citation statement)

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“…In this case, dimerization will activate PI3Ks. PI3Ks are a family of lipid kinases characterized by their ability to phosphorylate the hydroxyl group of the 3rd position on the inositol ring of phosphatidylinositol [107]. PI3Ks contain two domains: one P110 and one P85 domain.…”

Section: Pten-mediated Signalingmentioning

confidence: 99%

Cancer resistance via the downregulation of the tumor suppressors RKIP and PTEN expressions: therapeutic implications

Moghaddam

Vivarelli

Falzone

et al. 2023

Exploration of Targeted Anti-Tumor Therapy

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The Raf kinase inhibitor protein (RKIP) has been reported to be underexpressed in many cancers and plays a role in the regulation of tumor cells’ survival, proliferation, invasion, and metastasis, hence, a tumor suppressor. RKIP also regulates tumor cell resistance to cytotoxic drugs/cells. Likewise, the tumor suppressor, phosphatase and tensin homolog (PTEN), which inhibits the phosphatidylinositol 3 kinase (PI3K)/AKT pathway, is either mutated, underexpressed, or deleted in many cancers and shares with RKIP its anti-tumor properties and its regulation in resistance. The transcriptional and posttranscriptional regulations of RKIP and PTEN expressions and their roles in resistance were reviewed. The underlying mechanism of the interrelationship between the signaling expressions of RKIP and PTEN in cancer is not clear. Several pathways are regulated by RKIP and PTEN and the transcriptional and post-transcriptional regulations of RKIP and PTEN is significantly altered in cancers. In addition, RKIP and PTEN play a key role in the regulation of tumor cells response to chemotherapy and immunotherapy. In addition, molecular and bioinformatic data revealed crosstalk signaling networks that regulate the expressions of both RKIP and PTEN. These crosstalks involved the mitogen-activated protein kinase (MAPK)/PI3K pathways and the dysregulated nuclear factor-kappaB (NF-κB)/Snail/Yin Yang 1 (YY1)/RKIP/PTEN loop in many cancers. Furthermore, further bioinformatic analyses were performed to investigate the correlations (positive or negative) and the prognostic significance of the expressions of RKIP or PTEN in 31 different human cancers. These analyses were not uniform and only revealed that there was a positive correlation between the expression of RKIP and PTEN only in few cancers. These findings demonstrated the existence of signaling cross-talks between RKIP and PTEN and both regulate resistance. Targeting either RKIP or PTEN (alone or in combination with other therapies) may be sufficient to therapeutically inhibit tumor growth and reverse the tumor resistance to cytotoxic therapies.

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Section: Pten-mediated Signalingmentioning

confidence: 99%