A Potential Combination of Targeting HSP90 and mTOR in Breast Cancer Cell Growth, Migration, and Invasion Through Inhibiting AKT Phosphorylation and F-actin Organization
Issued Date
2024-06-01
Resource Type
eISSN
17917530
Scopus ID
2-s2.0-85194992075
Pubmed ID
38821604
Journal Title
Anticancer research
Volume
44
Issue
6
Start Page
2555
End Page
2565
Rights Holder(s)
SCOPUS
Bibliographic Citation
Anticancer research Vol.44 No.6 (2024) , 2555-2565
Suggested Citation
Suwannalert P., Panpinyaporn P., Wantanachaisaeng P., Teeppaibul T., Khumsri W., Koomsang T., Payuhakrit W., Naktubtim C. A Potential Combination of Targeting HSP90 and mTOR in Breast Cancer Cell Growth, Migration, and Invasion Through Inhibiting AKT Phosphorylation and F-actin Organization. Anticancer research Vol.44 No.6 (2024) , 2555-2565. 2565. doi:10.21873/anticanres.17061 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/98666
Title
A Potential Combination of Targeting HSP90 and mTOR in Breast Cancer Cell Growth, Migration, and Invasion Through Inhibiting AKT Phosphorylation and F-actin Organization
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Corresponding Author(s)
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Abstract
BACKGROUND/AIM: Breast cancer is the most prevalent form of cancer among women worldwide, with a high mortality rate. While the most common cause of breast cancer death is metastasis, there is currently no potential treatment for patients at the metastatic stage. The present study investigated the potential of using a combination of HSP90 and mTOR inhibitor in the treatment of breast cancer cell growth, migration, and invasion. MATERIALS AND METHODS: Gene Expression Profiling Interactive Analysis (GEPIA) was used to investigate the gene expression profiles. Western blot analysis and fluorescence staining were used for protein expression and localization, respectively. MTT, wound healing, and transwell invasion assays were used for cell proliferation, migration, and invasion, respectively. RESULTS: GEPIA demonstrated that HSP90 expression was significantly higher in breast invasive carcinoma compared to other tumor types, and this expression correlated with mTOR levels. Treatment with 17-AAG, an HSP90 inhibitor, and Torkinib, an mTORC1/2 inhibitor, significantly inhibited cell proliferation. Moreover, combination treatment led to down-regulation of AKT. Morphological changes revealed a reduction in F-actin intensity, a marked reduction of YAP, with interference in nuclear localization. CONCLUSION: Targeting HSP90 and mTOR has the potential to suppress breast cancer cell growth and progression by disrupting AKT signaling and inhibiting F-actin polymerization. This combination treatment may hold promise as a therapeutic strategy for breast cancer treatment that ameliorates adverse effects of a single treatment.