Integrin Signaling in Cancer: Mechanotransduction, Stemness, Epithelial Plasticity, and Therapeutic Resistance

Cancer Cell, Journal Year: 2019, Volume and Issue: 35(3), P. 347 - 367

Published: March 1, 2019

Language: Английский

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Role of Mitochondria in Radiation Responses: Epigenetic, Metabolic, and Signaling Impacts

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(20), P. 11047 - 11047

Published: Oct. 13, 2021

Until recently, radiation effects have been considered to be mainly due nuclear DNA damage and their management by repair mechanisms. However, molecular biology studies reveal that the outcomes of exposures ionizing (IR) highly depend on activation regulation through other components organelles determine cell survival proliferation capacities. As typical epigenetic-regulated central power stations cells, mitochondria play an important pivotal role in those responses. They direct cellular metabolism, energy supply homeostasis as well radiation-induced signaling, death, immunological This review is focused how energy, dose quality IR affect mitochondria-dependent epigenetic functional control at tissue level. Low-dose appear associated with non-targeted involved genomic instability adaptive responses, whereas high-dose (>1 Gy) concern therapeutic long-term involving mitochondria-mediated innate immune Both quality. For example, increased efficacy high linear transfer particle radiotherapy, e.g., C-ion relies reduction anastasis, enhanced apoptosis immunogenic (antitumor)

Language: Английский

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Hypoxia, endoplasmic reticulum stress and chemoresistance: dangerous liaisons

Journal of Experimental & Clinical Cancer Research, Journal Year: 2021, Volume and Issue: 40(1)

Published: Jan. 11, 2021

Abstract Solid tumors often grow in a micro-environment characterized by < 2% O 2 tension. This condition, together with the aberrant activation of specific oncogenic patwhays, increases amount and activity hypoxia-inducible factor-1α (HIF-1α), transcription factor that controls up to 200 genes involved neoangiogenesis, metabolic rewiring, invasion drug resistance. Hypoxia also induces endoplasmic reticulum (ER) stress, condition triggers cell death, if cells are irreversibly damaged, or survival, stress is mild. chronic ER both induce chemoresistance. In this review we discuss multiple interconnected circuitries link hypoxic environment, We suggest hypoxia train select more adapted survive unfavorable conditions, activating pleiotropic mechanisms including apoptosis inhibition, anti-oxidant defences, drugs efflux. adaptative process unequivocally expands clones acquire resistance chemotherapy. believe pharmacological inhibitors HIF-1α modulators although low specificty anti-cancer efficacy when used as single agents, may be repurposed chemosensitizers against chemorefractory next future.

Language: Английский

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Hypoxia-Induced Cancer Cell Responses Driving Radioresistance of Hypoxic Tumors: Approaches to Targeting and Radiosensitizing

Cancers, Journal Year: 2021, Volume and Issue: 13(5), P. 1102 - 1102

Published: March 4, 2021

Within aggressive malignancies, there usually are the “hypoxic zones”—poorly vascularized regions where tumor cells undergo oxygen deficiency through inadequate blood supply. Besides, hypoxia may arise in tumors as a result of antiangiogenic therapy or transarterial embolization. Adapting to hypoxia, acquire hypoxia-resistant phenotype with characteristic alterations signaling, gene expression and metabolism. Both lack by itself hypoxia-responsive phenotypic modulations render more radioresistant, so that hypoxic serious challenge for radiotherapy. An understanding causes radioresistance would help develop novel ways overcoming this challenge. Molecular targets various approaches radiosensitizing considered present review. It is here analyzed how hypoxia-induced cellular responses involving hypoxia-inducible factor-1, heat shock transcription factor 1, proteins, glucose-regulated epigenetic regulators, autophagy, energy metabolism reprogramming, epithelial–mesenchymal transition exosome generation contribute be inhibited attenuating radioresistance. The pretreatments multitarget inhibition cancer cell adaptation seem promising approach sensitizing carcinomas, gliomas, lymphomas, sarcomas radiotherapy and, also, liver radioembolization.

Language: Английский

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Dissecting Tumor Growth: The Role of Cancer Stem Cells in Drug Resistance and Recurrence

Cancers, Journal Year: 2022, Volume and Issue: 14(4), P. 976 - 976

Published: Feb. 15, 2022

Emerging evidence suggests that a small subpopulation of cancer stem cells (CSCs) is responsible for initiation, progression, and metastasis cascade in tumors. CSCs share characteristics with normal cells, i.e., self-renewal differentiation potential, suggesting they can drive progression. Consequently, targeting to prevent tumor growth or regrowth might offer chance lead the fight against cancer. create their niche, specific area within tissue unique microenvironment sustains vital functions. Interactions between niches play critical role regulating CSCs' tumorigenesis. Differences observed frequency CSCs, due phenotypic plasticity many remain challenge therapeutics, since modulate transcriptional activities into more stem-like state protect themselves from destruction. This represents an essential step future therapeutic approaches. Regarding self-renewal, are modulated by same molecular pathways found such as Wnt/β-catenin signaling, Notch Hedgehog signaling. Another key characteristic resistance standard chemotherapy radiotherapy treatments, capacity rest quiescent state. review will analyze primary mechanisms involved CSC tumorigenesis, particular attention roles progression benign malignant diseases; examine perspectives on identification new markers better control well dissecting process.

Language: Английский

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GRP78 as a potential therapeutic target in cancer treatment: an updated review of its role in chemoradiotherapy resistance of cancer cells

Medical Oncology, Journal Year: 2025, Volume and Issue: 42(2)

Published: Jan. 18, 2025

Language: Английский

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Interplay between TRAP1 and Sirtuin-3 Modulates Mitochondrial Respiration and Oxidative Stress to Maintain Stemness of Glioma Stem Cells

Cancer Research, Journal Year: 2019, Volume and Issue: 79(7), P. 1369 - 1382

Published: Jan. 25, 2019

Glioblastoma (GBM) cancer stem cells (CSC) are primarily responsible for metastatic dissemination, resistance to therapy, and relapse of GBM, the most common aggressive brain tumor. Development maintenance CSCs require orchestrated metabolic rewiring adaptation a changing microenvironment. Here, we show that cooperative interplay between mitochondrial chaperone TRAP1 major mitochondria deacetylase sirtuin-3 (SIRT3) in glioma (GSC) increases respiratory capacity reduces production reactive oxygen species. This regulation endowed GSCs with plasticity, facilitated stress (particularly reduced nutrient supply), maintained "stemness." Inactivation or SIRT3 compromised their interdependent regulatory mechanisms, leading alterations, loss stemness, suppression tumor formation by GSC vivo. Thus, targeting mechanisms regulating may provide novel therapeutic option intractable patients GBM. SIGNIFICANCE: Discovery functional analysis TRAP1-SIRT3 complex identify potential target proteins glioblastoma treatment.

Language: Английский

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Hypoxia Dictates Metabolic Rewiring of Tumors: Implications for Chemoresistance

Cells, Journal Year: 2020, Volume and Issue: 9(12), P. 2598 - 2598

Published: Dec. 4, 2020

Hypoxia is a condition commonly observed in the core of solid tumors. The hypoxia-inducible factors (HIF) act as hypoxia sensors that orchestrate coordinated response increasing pro-survival and pro-invasive phenotype cancer cells, determine broad metabolic rewiring. These events favor tumor progression chemoresistance. increase glucose amino acid uptake, glycolytic flux, lactate production; alterations glutamine metabolism, tricarboxylic cycle, oxidative phosphorylation; high levels mitochondrial reactive oxygen species; modulation both fatty synthesis oxidation are hallmarks rewiring induced by hypoxia. This review discusses how metabolic-dependent (e.g., increased acidification microenvironment coupled with intracellular alkalinization, reduced metabolism), metabolic-independent expression drug efflux transporters, stemness maintenance, epithelial-mesenchymal transition) cooperate determining chemoresistance Specific modifiers, however, can reverse hypoxic areas more chemoresistant into typical chemosensitive cells. We propose these able to hypoxia-induced rewiring, potential chemosensitizer agents against refractory

Language: Английский

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Calreticulin—Multifunctional Chaperone in Immunogenic Cell Death: Potential Significance as a Prognostic Biomarker in Ovarian Cancer Patients

Cells, Journal Year: 2021, Volume and Issue: 10(1), P. 130 - 130

Published: Jan. 11, 2021

Immunogenic cell death (ICD) is a type of death, which has the hallmarks necroptosis and apoptosis, best characterized in malignant diseases. Chemotherapeutics, radiotherapy photodynamic therapy induce intracellular stress response pathways tumor cells, leading to secretion various factors belonging family damage-associated molecular patterns molecules, capable inducing adaptive immune response. One them calreticulin (CRT), an endoplasmic reticulum-associated chaperone. Its presence on surface dying cells serves as “eat me” signal for antigen presenting (APC). Engulfment by APCs results presentation tumor’s antigens cytotoxic T-cells production cytokines/chemokines, activate responsible killing. Thus, development ICD expression CRT can help standard eradicate cells. Here, we review physiological functions its involvement appearance disease. Moreover, also focus ability anti-cancer drugs ovarian cancer The second aim this work discuss summarize prognostic/predictive value patients.

Language: Английский

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HIF-1–regulated expression of calreticulin promotes breast tumorigenesis and progression through Wnt/β-catenin pathway activation

Proceedings of the National Academy of Sciences, Journal Year: 2021, Volume and Issue: 118(44)

Published: Oct. 27, 2021

Significance Breast cancer stem cells (BCSCs) have the property of infinite self-renewal. When these divide, they give rise to one BCSC and transient amplifying cell that can rapidly proliferate but only for a limited number divisions. Only BCSCs secondary (recurrent and/or metastatic) tumors. It is believed breast recurrence due survival small BCSCs. Because represent very minority within primary tumor, their unique characteristics may not be detected by bulk tumor analyses. are often located regions intratumoral hypoxia, hypoxia-inducible factors activate transcription genes promote specification maintenance.

Language: Английский

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