Identification of regulatory crosstalks between RKIP and BRCA1 tumor suppressors in healthy tissues and cancer (breast and ovarian): Therapeutic implications

Rama, Martina; Bonavida, Benjamin

doi:10.1016/b978-0-12-819612-0.00011-0

Cited by 1 publication

(3 citation statements)

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“…Androgen receptors (ARs) are another type of transcription factor that directly binds to and regulates RKIP transcription in prostate epithelial cells [57,58]. In order to determine whether ARs bind to the RKIP promoter, researchers used the androgen hormone, dihydrotestosterone (DHT), on prostate epithelial cells.…”

Section: Transcriptionalmentioning

confidence: 99%

“…By adding a methyl group to histones, histone methyltransferases can suppress the activity of certain genes and influence the type of cell an immature cell will ultimately become (cell fate determination) [64]. EZH2 functions by binding to the proximal E-box of the RKIP promoter, recruiting the suppressor of zeste 12 (Suz12), and inducing the tri-methylation of lysines 9 and 27 of histone 3 (H3-K27) [10,58]. The methylation of lysine amino acids on histones results in reduced transcription, and expression levels between RKIP and EZH2 were shown to have a negative correlation in breast and prostate cell lines as well as in clinical tissues [10].…”

Section: Epigeneticmentioning

confidence: 99%

“…The phosphorylation of RKIP of Ser153 inactivates the binding pocket of RKIP, thereby resulting in the release of Raf-1 and activation of MEK and ERK [52]. pRKIP has a higher affinity to GRK2, which normally acts as a negative regulator of the G protein coupled receptor (GPCR) [58,71]. The pRKIP dimerizes GRK2 and prevents it from inhibiting the GPCR cascade, resulting in enhanced MAPK signaling [34].…”

Section: Post-translationalmentioning

confidence: 99%

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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: Transcriptionalmentioning

confidence: 99%