Exploring the dual role of endoplasmic reticulum stress in urological cancers: Implications for tumor progression and cell death interactions

Journal of Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 18(4)

Published: Nov. 3, 2024

Abstract The endoplasmic reticulum (ER) is crucial for maintaining calcium balance, lipid biosynthesis, and protein folding. Disruptions in ER homeostasis, often due to the accumulation of misfolded or unfolded proteins, lead stress, which plays a significant role various diseases, especially cancer. Urological cancers, account high male mortality worldwide, pose persistent challenge their incurability tendency develop drug resistance. Among numerous dysregulated biological mechanisms, stress key factor progression treatment response these cancers. This review highlights dual aberrant activation urologic affecting both tumor growth therapeutic outcomes. While can support through pro‐survival autophagy, it primarily inhibits cancer via apoptosis pro‐death autophagy. Interestingly, paradoxically aid mechanisms such as exosome‐mediated immune evasion. Additionally, examines how pharmacological interventions, particularly with phytochemicals, stimulate stress‐mediated suppression. Key regulators, including PERK, IRE1α, ATF6, are discussed roles upregulating CHOP levels triggering apoptosis. In conclusion, deeper understanding urological cancers not only clarifies complex interactions between cellular but also provides new opportunities innovative strategies.

Language: Английский

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Identification of anoikis-related molecular patterns and the novel risk model to predict prognosis, tumor microenvironment infiltration and immunotherapy response in bladder cancer

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Nov. 27, 2024

Background Anoikis, a unique form of cell death, serves as vital part the organism's defense by preventing shedding cells from re-attaching to incorrect positions, and plays pivotal role in cancer metastasis. Nonetheless, specific mechanisms among anoikis, clinical prognosis tumor microenvironment (TME) bladder (BLCA) are insufficiently understood. Method BLCA patients were classified into different anoikis subtypes based on expression candidate anoikis-related genes (ARGs), differences clinicopathological features, TME, immune infiltration, checkpoints between two analyzed. Next, TCGA cohort randomized train test groups 1:1 ratio. Subsequently, model was constructed predict via utilizing univariate Cox, LASSO multivariate Cox analyses, validated internally externally. Moreover, relationships risk score clinicopathologic immunotherapy response, antitumor drug sensitivity also In addition, representative evaluated using immunohistochemistry specimens, lines, functional experiments performed determine biological behavior hub gene PLOD1. Result Two definite subgroups identified. Compared ARGcluster A, assigned B characterized an immunosuppressive worse prognosis. Then, model, including PLOD1, EHBP1, CSPG4, constructed, low-risk group better accurate nomogram built improve applicability combining age, stage Score. infiltration features differed significantly high- groups. We found that exhibited lower dysfunction exclusion score, higher immunophenoscore (IPS), had more immunotherapy. Eventually, levels three verified our experiment, knockdown PLOD1 could inhibit invasion migration abilities lines. Conclusion These results demonstrated new direction precision therapy for BLCA, indicated ARGs might be helpful predicting therapeutic targets BLCA.

Language: Английский

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Starvation-induced long non-coding RNAs are significant for prognosis evaluation of bladder cancer

Aging, Journal Year: 2022, Volume and Issue: 14(24), P. 10067 - 10080

Published: Dec. 20, 2022

Starving intratumoral microenvironment prominently alters genic profiles including long non-coding RNAs (lncRNAs), which further regulate bladder cancer (BCa) malignant biological properties, such as invasion and migration.Transcriptome RNA-sequencing data of 414 BCa tumor tissues 19 normal were obtained from TCGA database paired samples 132 patients. A chain in vitro validations qPCR, migration assays performed to reveal the clinical relevance AC011472.4 AL157895.1.A total 11 lncRNAs identified starvation-related lncRNAs, AL157895.1 relevant overall survival Besides, a risk score model was established based on levels AL157895.1. patients with higher divided into high-risk group usually mortality rate, but contrary. expressed highly cell lines tumour tissues, especially advanced grade, stage T-stage, while showed reversed result. Moreover, increased level remarkably correlated muscle status distant metastasis. SiRNAs-mediated silence respectively diminished properties cells.In this study, we highlight significant roles evaluating prognoses validate their correlation various parameters. These findings provide an appropriate for decision making.

Language: Английский

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