Deregulation of <scp>HSF1</scp>‐mediated endoplasmic reticulum unfolded protein response promotes cisplatin resistance in lung cancer cells

Zhang, Min; Duan, Xiaoyu; Wang, Lu; Wen, Jing; Fang, Pingfei

doi:10.1111/febs.16709

Cited by 3 publications

(2 citation statements)

References 46 publications

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“…Cells were treated with 33.3 mM glucose for 24 h to induce apoptosis as reported before 34 . Flow cytometry was used for apoptosis analysis as reported before 47 . In brief, attached cells were harvested by trypsin treatment and washed with cold PBS containing 0.5% BSA (bovine serum albumin) for 3 times by centrifuge at 200 RFC.…”

Section: Methodsmentioning

confidence: 99%

MRPS6 modulates glucose-stimulated insulin secretion in mouse islet cells through mitochondrial unfolded protein response

Lin,

Yu,

Lin

et al. 2023

Sci Rep

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Lack of efficient insulin secretion from the pancreas can lead to impaired glucose tolerance (IGT), prediabetes, and diabetes. We have previously identified two IGT-associated single nucleotide polymorphisms (SNPs) rs62212118 and rs13052524 located at two overlapping genes: MRPS6 and SLC5A3. In this study, we show that MRPS6 but not SLC5A3 regulates glucose-stimulated insulin secretion (GSIS) in primary human β-cell and a mouse pancreatic insulinoma β-cell line. Data mining and biochemical studies reveal that MRPS6 is positively regulated by the mitochondrial unfolded protein response (UPRmt), but feedback inhibits UPRmt. Disruption of such feedback by MRPS6 knockdown causes UPRmt hyperactivation in high glucose conditions, hence elevated ROS levels, increased apoptosis, and impaired GSIS. Conversely, MRPS6 overexpression reduces UPRmt, mitigates high glucose-induced ROS levels and apoptosis, and enhances GSIS in an ATF5-dependent manner. Consistently, UPRmt up-regulation or down-regulation by modulating ATF5 expression is sufficient to decrease or increase GSIS. The negative role of UPRmt in GSIS is further supported by analysis of public transcriptomic data from murine islets. In all, our studies identify MRPS6 and UPRmt as novel modulators of GSIS and apoptosis in β-cells, contributing to our understanding of the molecular and cellular mechanisms of IGT, prediabetes, and diabetes.

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Section: Methodsmentioning

confidence: 99%

MRPS6 modulates glucose-stimulated insulin secretion in mouse islet cells through mitochondrial unfolded protein response

Lin,

Yu,

Lin

et al. 2023

Sci Rep

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show abstract

“…Furthermore, UPR can directly mediate apoptosis. In lung cancer, UPR induces apoptosis by engaging caspase 2 and DNA repair mechanisms, with HSF1’s participation ( Gaddameedhi and Chatterjee, 2009 ; Zhang et al, 2023 ).…”

Section: Complex Role Of Upr In Tumor Microenvironment: From Chemores...mentioning

confidence: 99%

Endoplasmic reticulum stress and quality control in relation to cisplatin resistance in tumor cells

Mu,

Zhi,

Zhou

et al. 2024

Front. Pharmacol.

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The endoplasmic reticulum (ER) is a crucial organelle that orchestrates key cellular functions like protein folding and lipid biosynthesis. However, it is highly sensitive to disturbances that lead to ER stress. In response, the unfolded protein response (UPR) activates to restore ER homeostasis, primarily through three sensors: IRE1, ATF6, and PERK. ERAD and autophagy are crucial in mitigating ER stress, yet their dysregulation can lead to the accumulation of misfolded proteins. Cisplatin, a commonly used chemotherapy drug, induces ER stress in tumor cells, activating complex signaling pathways. Resistance to cisplatin stems from reduced drug accumulation, activation of DNA repair, and anti-apoptotic mechanisms. Notably, cisplatin-induced ER stress can dualistically affect tumor cells, promoting either survival or apoptosis, depending on the context. ERAD is crucial for degrading misfolded proteins, whereas autophagy can protect cells from apoptosis or enhance ER stress-induced apoptosis. The complex interaction between ER stress, cisplatin resistance, ERAD, and autophagy opens new avenues for cancer treatment. Understanding these processes could lead to innovative strategies that overcome chemoresistance, potentially improving outcomes of cisplatin-based cancer treatments. This comprehensive review provides a multifaceted perspective on the complex mechanisms of ER stress, cisplatin resistance, and their implications in cancer therapy.

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Advances in PET imaging of cancer

et al. 2023

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Deregulation of HSF1‐mediated endoplasmic reticulum unfolded protein response promotes cisplatin resistance in lung cancer cells

Cited by 3 publications

References 46 publications

MRPS6 modulates glucose-stimulated insulin secretion in mouse islet cells through mitochondrial unfolded protein response

MRPS6 modulates glucose-stimulated insulin secretion in mouse islet cells through mitochondrial unfolded protein response

Endoplasmic reticulum stress and quality control in relation to cisplatin resistance in tumor cells

Advances in PET imaging of cancer

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