Hsp90 facilitates acquired drug resistance of tumor cells through cholesterol modulation however independent of tumor progression

Kumar, Pankaj; Devaki, Bharath; Jonnala, Ujwal Kumar; Subbarao, Sreedhar Amere

doi:10.1016/j.bbamcr.2020.118728

Cited by 4 publications

(15 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In agreement with our earlier findings, we observed enhanced drug efflux activity in response to 17AAG treatment (Figure 1C). Further, we also demonstrated that P‐glycoprotein (P‐gp) majorly contributes to the acquired drug resistance, therefore, in the present study, the drug efflux activity that we mentioned is pertinent to P‐gp activity 23 …”

Section: Resultssupporting

confidence: 60%

“…Our earlier in vitro findings with drug-resistant cells have indicated that inhibiting metastasis will not interfere with the drug efflux activity. 23 MMPs to interfere with tumor metastasis has emerged. However, the current MMP inhibitors aim the conserved catalytic site, thus lacks the individual MMP specificity and selectivity.…”

Section: Discussionmentioning

confidence: 99%

“…Quercetin at a final concentration of 10 μM (#Q4951‐10G, Sigma‐Aldrich) was used to inhibit the stress response 26 . The drug‐resistant cells were prepared by treating KB Parental cells with lower to higher concentrations of vinblastine (0.5–2.0 μM, Sigma‐Aldrich, V1377‐5MG), and its combination with cisplatin (0.5–2.0 μM, Sigma‐Aldrich, C2210000) for 60 passages and named KBvb and KBvbcp (drug‐resistant), respectively 23 …”

Section: Methodsmentioning

confidence: 99%

“…Cells were washed with 1× PBS and scraped into 1 mL of PBS on ice and analyzed using a flow cytometer (Beckman Coulter, Gallios). The efflux ratio was calculated by the mean channel value of Cyclosporin A/mean channel value of treatments as per our previous publication 23 …”

Section: Methodsmentioning

confidence: 99%

“…Further, we also demonstrated that P-glycoprotein (P-gp) majorly contributes to the acquired drug resistance, therefore, in the present study, the drug efflux activity that we mentioned is pertinent to P-gp activity. 23 Since induced stress response is grossly implicated in cellular adaptations that make tumor cells to evolve, 31 we have examined the heat shock response or stress response through induced Hsp synthesis in presence and absence of quercetin, a drug that interferes with the intracellular stress response. 26 In agreement with previous reports that Hsp90 inhibitors can induce stress response via the feedback loop mechanism by inducing the transcription of heat shock genes, 23 we have observed induced expressions of Hsp70, Hsp90α, and…”

Section: The Drug-resistant Cells Display Induced Mmp Expression Anmentioning

confidence: 99%

See 4 more Smart Citations

The matrix metalloproteinase 7 (MMP7) links Hsp90 chaperone with acquired drug resistance and tumor metastasis

Kumar

Siripini²,

Sreedhar

2020

Cancer Reports

Self Cite

View full text Add to dashboard Cite

Background: Cancer emergence is associated with a series of cellular transformations that include acquired drug resistance followed by tumor metastasis. Matrix metalloproteinases (MMPs) and Hsp90 chaperone are implicated in tumor progression, however, they are not studied in the context of drug resistance. Aims: In the present study, we aimed at understanding the cross-talk between acquired drug resistance and tumor progression, linking MMP7 and Hsp90. Methods and results: We have developed an in vitro model system for acquired drug resistance and studied the correlation between MMP7 and Hsp90. We demonstrate that enhanced drug efflux activity correlates with the induced expression and activity of MMP7, and enhanced metastatic potential of cells, however, in Hsp90-dependent manner. The MMP7 overexpression alone could enhance the drug efflux activity marginally, and metastasis significantly. However, challenging these cells with 17AAG has significantly increased the drug efflux activity and, in contrast, decreased the metastatic potential. Evaluating our in vitro findings in mice xenografts revealed that MMP7 overexpression facilitates altered homing properties. However, these cells, in response to 17AAG treatment, exhibited increased localized tumor growth but decreased tumor metastasis. Conclusion: We demonstrated a cross-talk between Hsp90 and MMP7 in regulating the acquired drug resistance and tumor progression. Our findings provide novel insights on targeting drug resistant-tumors.

show abstract

Section: Resultssupporting

confidence: 60%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: The Drug-resistant Cells Display Induced Mmp Expression Anmentioning

confidence: 99%

See 3 more Smart Citations

The matrix metalloproteinase 7 (MMP7) links Hsp90 chaperone with acquired drug resistance and tumor metastasis

Kumar

Siripini²,

Sreedhar

2020

Cancer Reports

Self Cite

View full text Add to dashboard Cite

show abstract

Osthole Increases the Sensitivity of Liver Cancer to Sorafenib by Inhibiting Cholesterol Metabolism

Fan

Huang

Zhao

et al. 2022

Nutrition and Cancer

View full text Add to dashboard Cite

Heat Shock Proteins, a Double-Edged Sword: Significance in Cancer Progression, Chemotherapy Resistance and Novel Therapeutic Perspectives

Kunachowicz,

Król-Kulikowska,

Raczycka

et al. 2024

Cancers

View full text Add to dashboard Cite

Heat shock proteins (Hsps) are involved in one of the adaptive mechanisms protecting cells against environmental and metabolic stress. Moreover, the large role of these proteins in the carcinogenesis process, as well as in chemoresistance, was noticed. This review aims to draw attention to the possibilities of using Hsps in developing new cancer therapy methods, as well as to indicate directions for future research on this topic. In order to discuss this matter, a thorough review of the latest scientific literature was carried out, taking into account the importance of selected proteins from the Hsp family, including Hsp27, Hsp40, Hsp60, Hsp70, Hsp90 and Hsp110. One of the more characteristic features of all Hsps is that they play a multifaceted role in cancer progression, which makes them an obvious target for modern anticancer therapy. Some researchers emphasize the importance of directly inhibiting the action of these proteins. In turn, others point to their possible use in the design of cancer vaccines, which would work by inducing an immune response in various types of cancer. Due to these possibilities, it is believed that the use of Hsps may contribute to the progress of oncoimmunology, and thus help in the development of modern anticancer therapies, which would be characterized by higher effectiveness and lower toxicity to the patients.

show abstract

Hsp90 facilitates acquired drug resistance of tumor cells through cholesterol modulation however independent of tumor progression

Cited by 4 publications

References 65 publications

The matrix metalloproteinase 7 (MMP7) links Hsp90 chaperone with acquired drug resistance and tumor metastasis

The matrix metalloproteinase 7 (MMP7) links Hsp90 chaperone with acquired drug resistance and tumor metastasis

Osthole Increases the Sensitivity of Liver Cancer to Sorafenib by Inhibiting Cholesterol Metabolism

Heat Shock Proteins, a Double-Edged Sword: Significance in Cancer Progression, Chemotherapy Resistance and Novel Therapeutic Perspectives

Contact Info

Product

Resources

About