Rho GTPases in cancer radiotherapy and metastasis

Zeng, Ruijie; Zheng, Chunwen; Chen, Wan-Xian; Xu, Li‐Yan; Li, En‐Min

doi:10.1007/s10555-020-09923-5

Cited by 17 publications

(10 citation statements)

References 146 publications

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“…Rac1 plays roles in tumorigenesis, tumor progression, EMT and metastasis of bladder cancer cells. The GTPase has been also implicated in other hallmarks of cancer, notably in stemness, immune escape and drug resistance [ 30 , 111 ]. These aspects have not been significantly studied in the frame of bladder cancer.…”

Section: Rac1 In Bladder Cancermentioning

confidence: 99%

Rac1 as a Target to Treat Dysfunctions and Cancer of the Bladder

Sauzeau

Beignet²,

Bailly

2022

Biomedicines

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Bladder pathologies, very common in the aged population, have a considerable negative impact on quality of life. Novel targets are needed to design drugs and combinations to treat diseases such as overactive bladder and bladder cancers. A promising new target is the ubiquitous Rho GTPase Rac1, frequently dysregulated and overexpressed in bladder pathologies. We have analyzed the roles of Rac1 in different bladder pathologies, including bacterial infections, diabetes-induced bladder dysfunctions and bladder cancers. The contribution of the Rac1 protein to tumorigenesis, tumor progression, epithelial-mesenchymal transition of bladder cancer cells and their metastasis has been analyzed. Small molecules selectively targeting Rac1 have been discovered or designed, and two of them—NSC23766 and EHT 1864—have revealed activities against bladder cancer. Their mode of interaction with Rac1, at the GTP binding site or the guanine nucleotide exchange factors (GEF) interaction site, is discussed. Our analysis underlines the possibility of targeting Rac1 with small molecules with the objective to combat bladder dysfunctions and to reduce lower urinary tract symptoms. Finally, the interest of a Rac1 inhibitor to treat advanced chemoresistance prostate cancer, while reducing the risk of associated bladder dysfunction, is discussed. There is hope for a better management of bladder pathologies via Rac1-targeted approaches.

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Section: Rac1 In Bladder Cancermentioning

confidence: 99%

Rac1 as a Target to Treat Dysfunctions and Cancer of the Bladder

Sauzeau

Beignet²,

Bailly

2022

Biomedicines

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“…The results revealed that the KEGG-p53, PID-PLK1, Notch, Rho-GTPase, KEGG-TGFβ, and Wnt signaling pathways were differentially enriched in the KIF11-high group. Accumulating evidence has indicated that these signaling pathways regulate many aspects of cancer biology (32)(33)(34)(35)(36)(37).…”

Section: Discussionmentioning

confidence: 99%

KIF11 is a potential prognostic biomarker and therapeutic target for adrenocortical carcinoma

Zhou¹,

Chen²,

Li³

et al. 2023

Transl Androl Urol

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Background: Adrenocortical carcinoma (ACC) is a rare endocrine neoplasia with poor prognosis.Emerging evidence suggests that kinesin family member 11 (KIF11) protein is overexpressed in several tumors and associated with the onset and progression of certain types of cancer; however, its biological functions and mechanisms in ACC progression have not been studied yet. Therefore, this study evaluated the clinical significance and therapeutic potential of the KIF11 protein in ACC. Methods:The Cancer Genome Atlas (TCGA) database (n=77) and Genotype Tissue Expression (GTEx) database (n=128) were utilized to explore the expression of KIF11 in ACC and normal adrenal tissues.The TCGA datasets were then data mined and statistically analyzed. R survival analysis and univariate and multivariate Cox regression analyses were used to evaluate the effect of KIF11 expression on the survival rates, and a nomogram was used to predict its impact on prognosis. The clinical data from 30 ACC patients' from Xiangya Hospital were also analyzed. The effects of KIF11 on the proliferation and invasion of ACC NCI-H295R were further validated in vitro.Results: Analytical data from the TCGA and GTEx databases showed that KIF11 expression was upregulated in ACC tissues and associated with T (primary tumor), and M (metastasis) and stages of tumor progression. Increased KIF11 expression was significantly associated with shorter overall survival, diseasespecific survival, and progression-free intervals. Clinical data from Xiangya Hospital illustrated that increased KIF11 had a significantly positive correlation with shorter overall survival, T and pathological stages, and tumor recurrence risk. Monastrol, a specific inhibitor of KIF11, was further confirmed to significantly inhibit the proliferation and invasion of ACC NCI-H295R cell in vitro. The nomogram demonstrated KIF11 was an excellent predictive biomarker in patients with ACC. Conclusions:The findings demonstrate that KIF11 could be a predictor of poor prognosis and thus possibly serve as a novel therapeutic target for ACC.

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“…However, Rho GTPase inhibitors are not currently available in clinical practice for any disorders. Because of the extensive involvement of Rho GTPases in basic fundamental processes, such as glucose uptake, immune response, and organ development, general inhibition of Rho GTPases would exert unexpected and even detrimental effects on physiological activities ( Zeng et al., 2020 ). Recent developments in biotechnologies, including liposomes, exosomes, nanoparticles, and polymeric micelles, provide promising modalities for targeted therapy of rheumatic diseases ( Feng and Chen, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

Rho GTPase signaling in rheumatic diseases

et al. 2022

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Summary Rho guanosine triphosphatase (GTPases), as molecular switches, have been identified to be dysregulated and involved in the pathogenesis of various rheumatic diseases, mainly including rheumatoid arthritis, osteoarthritis, systemic sclerosis, and systemic lupus erythematosus. Downstream pathways involving multiple types of cells, such as fibroblasts, chondrocytes, synoviocytes, and immunocytes are mediated by activated Rho GTPases to promote pathogenesis. Targeted therapy via inhibitors of Rho GTPases has been implicated in the treatment of rheumatic diseases, demonstrating promising effects. In this review, the effects of Rho GTPases in the pathogenesis of rheumatic diseases are summarized, and the Rho GTPase-mediated pathways are elucidated. Therapeutic strategies using Rho GTPase inhibitors in rheumatic diseases are also discussed to provide insights for further exploration of targeted therapy in preclinical studies and clinical practice. Future directions on studies of Rho GTPases in rheumatic diseases based on current understandings are provided.

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Rho GTPases in cancer radiotherapy and metastasis

Cited by 17 publications

References 146 publications

Rac1 as a Target to Treat Dysfunctions and Cancer of the Bladder

Rac1 as a Target to Treat Dysfunctions and Cancer of the Bladder

KIF11 is a potential prognostic biomarker and therapeutic target for adrenocortical carcinoma

Rho GTPase signaling in rheumatic diseases

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