TRPV1 inhibition overcomes cisplatin resistance by blocking autophagy-mediated hyperactivation of EGFR signaling pathway

Oh, Se Jin; Lim, Jin‐Ho; Son, Min Kyu; Ahn, Ji Hoon; Song, Kwon‐Ho; Lee, Hyo‐Jung; Kim, Su Yeon; Cho, Eun Ho; Chung, Joon‐Yong; Cho, Hanbyoul; Kim, Hyosun; Kim, Jae-Hoon; Park, Jooyoung; Choi, Jungmin; Hwang, Sun Wook; Kim, Tae Woo

doi:10.1038/s41467-023-38318-7

Cited by 13 publications

(2 citation statements)

References 62 publications

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“…However, cisplatin resistance is a common issue in bladder cancer treatment, often leading to poor treatment efficacy [ 22 ]. Several studies have revealed that autophagy plays a crucial role in mediating cisplatin resistance [ 23 , 24 , 25 ], and inhibiting autophagy can enhance the sensitivity of bladder cancer cells to cisplatin [ 13 ]. In this study, we successfully developed cisplatin-resistant T24/DDP cell lines derived from bladder cancer cells.…”

Section: Discussionmentioning

confidence: 99%

SIRT1 Promotes Cisplatin Resistance in Bladder Cancer via Beclin1 Deacetylation-Mediated Autophagy

Sun,

Liu,

Tong

et al. 2023

Cancers

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Autophagy-dependent cisplatin resistance poses a challenge in bladder cancer treatment. SIRT1, a protein deacetylase, is involved in autophagy regulation. However, the precise mechanism through which SIRT1 mediates cisplatin resistance in bladder cancer via autophagy remains unclear. In this study, we developed a cisplatin-resistant T24/DDP cell line to investigate this mechanism. The apoptosis rate and cell viability were assessed using flow cytometry and the CCK8 method. The expression levels of the relevant RNA and protein were determined using RT-qPCR and a Western blot analysis, respectively. Immunoprecipitation was utilized to validate the interaction between SIRT1 and Beclin1, as well as to determine the acetylation level of Beclin1. The findings indicated the successful construction of the T24/DDP cell line, which exhibited autophagy-dependent cisplatin resistance. Inhibiting autophagy significantly reduced the drug resistance index of these cells. The T24/DDP cell line showed a high SIRT1 expression level. The overexpression of SIRT1 activated autophagy, thereby further promoting cisplatin resistance in the T24/DDP cell line. Conversely, inhibiting autophagy counteracted the cisplatin-resistance-promoting effects of SIRT1. Silencing SIRT1 led to increased acetylation of Beclin1, the inhibition of autophagy, and a reduction in the cisplatin resistance of the T24/DDP cell line. Introducing a double mutation (lysine 430 and 437 to arginine, 2KR) in Beclin-1 inhibited acetylation and activated autophagy, effectively reversing the decreased cisplatin resistance resulting from SIRT1 silencing. In summary, our study elucidated that SIRT1 promotes cisplatin resistance in human bladder cancer T24 cells through Beclin1-deacetylation-mediated autophagy activation. These findings suggest a potential new strategy for reversing cisplatin resistance in bladder cancer.

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Section: Discussionmentioning

confidence: 99%

SIRT1 Promotes Cisplatin Resistance in Bladder Cancer via Beclin1 Deacetylation-Mediated Autophagy

Sun,

Liu,

Tong

et al. 2023

Cancers

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“…To address these challenges, studies have focused on combination treatments. One study has shown that cisplatin susceptibility in tumors can be achieved by the inhibition of transient receptor potential vanilloid 1 (TRPV1), which is a nonselective cationic channel regulating Ca 2+ influx [148]. Interestingly, various tissues like the brain, kidney, bronchial epithelial cells and others show the wide expression of TRPV1, and these organs are damaged by the severe cytokine storm of COVID-19.…”

Section: Future Perspectives: Potential Aims and Experimental Methodsmentioning

confidence: 99%

Developmental Impacts of Epigenetics and Metabolism in COVID-19

Naik,

Patel,

Sen

2024

JDB

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Developmental biology is intricately regulated by epigenetics and metabolism but the mechanisms are not completely understood. The situation becomes even more complicated during diseases where all three phenomena are dysregulated. A salient example is COVID-19, where the death toll exceeded 6.96 million in 4 years, while the virus continues to mutate into different variants and infect people. Early evidence during the pandemic showed that the host’s immune and inflammatory responses to COVID-19 (like the cytokine storm) impacted the host’s metabolism, causing damage to the host’s organs and overall physiology. The involvement of angiotensin-converting enzyme 2 (ACE2), the pivotal host receptor for the SARS-CoV-2 virus, was identified and linked to epigenetic abnormalities along with other contributing factors. Recently, studies have revealed stronger connections between epigenetics and metabolism in COVID-19 that impact development and accelerate aging. Patients manifest systemic toxicity, immune dysfunction and multi-organ failure. Single-cell multiomics and other state-of-the-art high-throughput studies are only just beginning to demonstrate the extent of dysregulation and damage. As epigenetics and metabolism directly impact development, there is a crucial need for research implementing cutting-edge technology, next-generation sequencing, bioinformatics analysis, the identification of biomarkers and clinical trials to help with prevention and therapeutic interventions against similar threats in the future.

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Loss-of-function mutation of REV1 (p.R704Q) mediates cetuximab primary resistance by activating autophagy in RAS-wild type metastatic colorectal cancer

Zhu,

Ding,

et al. 2024

Cancer Letters

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TRPV1 inhibition overcomes cisplatin resistance by blocking autophagy-mediated hyperactivation of EGFR signaling pathway

Cited by 13 publications

References 62 publications

SIRT1 Promotes Cisplatin Resistance in Bladder Cancer via Beclin1 Deacetylation-Mediated Autophagy

SIRT1 Promotes Cisplatin Resistance in Bladder Cancer via Beclin1 Deacetylation-Mediated Autophagy

Developmental Impacts of Epigenetics and Metabolism in COVID-19

Loss-of-function mutation of REV1 (p.R704Q) mediates cetuximab primary resistance by activating autophagy in RAS-wild type metastatic colorectal cancer

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