CD147: an integral and potential molecule to abrogate hallmarks of cancer DOI Creative Commons
Alphonce M. K. Nyalali,

Angela U. Leonard,

Yongxiang Xu

и другие.

Frontiers in Oncology, Год журнала: 2023, Номер 13

Опубликована: Ноя. 7, 2023

CD147 also known as EMMPRIN, basigin, and HAb18G, is a single-chain type I transmembrane protein shown to be overexpressed in aggressive human cancers of CNS, head neck, breasts, lungs, gastrointestinal, genitourinary, skin, hematological, musculoskeletal. In these malignancies, the molecule integral diverse but complimentary hallmarks cancer: it pivotal cancerous proliferative signaling, growth propagation, cellular survival, replicative immortality, angiogenesis, metabolic reprogramming, immune evasion, invasion, metastasis. has regulatory functions cancer-enabling characteristics such DNA damage response (DDR) evasion. These neoplastic are executed through numerous sometimes overlapping molecular pathways: transduces signals from upstream molecules or ligands cyclophilin A (CyPA), CD98, S100A9; activates repertoire downstream pathways including matrix metalloproteinases (MMPs)-2,3,9, hypoxia-inducible factors (HIF)-1/2α, PI3K/Akt/mTOR/HIF-1α, ATM/ATR/p53; an indispensable chaperone regulator monocarboxylate, fatty acid, amino acid transporters. Interestingly, induced loss prevents reverses acquired cancer diseases. Silencing Cd147 alleviates resistance chemoradiotherapy exhibited by malignant tumors like carcinomas breast, lung, pancreas, liver, gastric, colon, ovary, cervix, prostate, urinary bladder, glioblastoma, melanoma. Targeting antigen chimeric induced-chimeric T cell antibody therapies safer more effective. Moreover, incorporating anti-CD147 monoclonal antibodies chemoradiotherapy, oncolytic viral therapy, virus-based-gene increases effectiveness reduces on off-target toxicity. This study advocates expedition expansion further exploiting evidence experimental studies that modulate features strive translate them into clinical practice alleviate emergency propagation cancer, well associated social consequences.

Язык: Английский

Hypoxia-inducible factors: cancer progression and clinical translation DOI Creative Commons
Elizabeth E. Wicks, Gregg L. Semenza

Journal of Clinical Investigation, Год журнала: 2022, Номер 132(11)

Опубликована: Май 31, 2022

Hypoxia-inducible factors (HIFs) are master regulators of oxygen homeostasis that match O2 supply and demand for each the 50 trillion cells in adult human body. Cancer co-opt this homeostatic system to drive cancer progression. HIFs activate transcription thousands genes mediate angiogenesis, stem cell specification, motility, epithelial-mesenchymal transition, extracellular matrix remodeling, glucose lipid metabolism, immune evasion, invasion, metastasis. In Review, mechanisms consequences HIF activation presented. The current status future prospects small-molecule inhibitors use as therapeutics discussed.

Язык: Английский

Процитировано

358
Define cancer-associated fibroblasts (CAFs) in the tumor microenvironment: new opportunities in cancer immunotherapy and advances in clinical trials DOI Creative Commons
Hao Zhang,

Xinghai Yue,

Zhe Chen

и другие.

Molecular Cancer, Год журнала: 2023, Номер 22(1)

Опубликована: Окт. 2, 2023

Abstract Despite centuries since the discovery and study of cancer, cancer is still a lethal intractable health issue worldwide. Cancer-associated fibroblasts (CAFs) have gained much attention as pivotal component tumor microenvironment. The versatility sophisticated mechanisms CAFs in facilitating progression been elucidated extensively, including promoting angiogenesis metastasis, inducing drug resistance, reshaping extracellular matrix, developing an immunosuppressive Owing to their robust tumor-promoting function, are considered promising target for oncotherapy. However, highly heterogeneous group cells. Some subpopulations exert inhibitory role growth, which implies that CAF-targeting approaches must be more precise individualized. This review comprehensively summarize origin, phenotypical, functional heterogeneity CAFs. More importantly, we underscore advances strategies clinical trials CAF various cancers, also progressions immunotherapy.

Язык: Английский

Процитировано

170
Targeting fatty acid synthase modulates sensitivity of hepatocellular carcinoma to sorafenib via ferroptosis DOI Creative Commons
Yan Li, Wenjuan Yang, Yuanyuan Zheng

и другие.

Journal of Experimental & Clinical Cancer Research, Год журнала: 2023, Номер 42(1)

Опубликована: Янв. 6, 2023

Sorafenib resistance is a key impediment to successful treatment of patients with advanced hepatocellular carcinoma (HCC) and recent studies have reported reversal drug by targeting ferroptosis. The present study aimed explore the association fatty acid synthase (FASN) sorafenib via regulation ferroptosis provide novel strategy overcome HCC patients.Intracellular levels lipid peroxides, glutathione, malondialdehyde, Fe2+ were measured as indicators status. Biological information analyses, immunofluorescence assays, western blot co-immunoprecipitation analyses conducted elucidate functions FASN in HCC. Both vitro vivo examine antitumor effects combination orlistat CalcuSyn software was used calculate index.Solute carrier family 7 member 11 (SLC7A11) found play an important role mediating resistance. up-regulation antagonize SLC7A11-mediated thereby promoted Mechanistically, enhanced sorafenib-induced binding hypoxia-inducible factor 1-alpha (HIF1α), promoting HIF1α nuclear translocation, inhibiting ubiquitination proteasomal degradation HIF1α, subsequently enhancing transcription SLC7A11. Orlistat, inhibitor FASN, had significant synergistic reversed both vivo.Targeting FASN/HIF1α/SLC7A11 pathway resensitized cells sorafenib. superior sorafenib-resistant cells.

Язык: Английский

Процитировано

93
Hypoxia, oxidative stress, and the interplay of HIFs and NRF2 signaling in cancer DOI Creative Commons

Taegeun Bae,

Steffanus Pranoto Hallis, Mi‐Kyoung Kwak

и другие.

Experimental & Molecular Medicine, Год журнала: 2024, Номер 56(3), С. 501 - 514

Опубликована: Март 1, 2024

Abstract Oxygen is crucial for life and acts as the final electron acceptor in mitochondrial energy production. Cells adapt to varying oxygen levels through intricate response systems. Hypoxia-inducible factors (HIFs), including HIF-1α HIF-2α, orchestrate cellular hypoxic response, activating genes increase supply reduce expenditure. Under conditions of excess resulting oxidative stress, nuclear factor erythroid 2-related 2 (NRF2) activates hundreds oxidant removal adaptive cell survival. Hypoxia stress are core hallmarks solid tumors activated HIFs NRF2 play pivotal roles tumor growth progression. The complex interplay between hypoxia within microenvironment adds another layer intricacy HIF signaling This review aimed elucidate dynamic changes functions pathways emphasizing their implications milieu. Additionally, this explored elaborate NRF2, providing insights into significance these interactions development novel cancer treatment strategies.

Язык: Английский

Процитировано

71
TGF-β, EMT, and resistance to anti-cancer treatment DOI Creative Commons

Xuecong Wang,

Pieter J.A. Eichhorn, Jean Paul Thiery

и другие.

Seminars in Cancer Biology, Год журнала: 2023, Номер 97, С. 1 - 11

Опубликована: Ноя. 8, 2023

Transforming growth factor-β (TGF-β) signaling regulates cell-specific programs involved in embryonic development, wound-healing, and immune homeostasis. Yet, during tumor progression, these TGF-β-mediated are altered, leading to epithelial cell plasticity a reprogramming of cells into mesenchymal lineages through epithelial-to-mesenchymal transition (EMT), critical developmental program morphogenesis organogenesis. These changes, turn, lead enhanced carcinoma invasion, metastasis, differentiation, evasion, chemotherapy resistance. Here, we discuss EMT as one the associated with influence exerted by TGF-β on status function. We further explore composition other populations within microenvironment, consider relevant outcomes related cancer treatment

Язык: Английский

Процитировано

61
Cellular succinate metabolism and signaling in inflammation: implications for therapeutic intervention DOI Creative Commons
Hong Huang,

Gejing Li,

Yini He

и другие.

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Июнь 11, 2024

Succinate, traditionally viewed as a mere intermediate of the tricarboxylic acid (TCA) cycle, has emerged critical mediator in inflammation. Disruptions within TCA cycle lead to an accumulation succinate mitochondrial matrix. This excess subsequently diffuses into cytosol and is released extracellular space. Elevated cytosolic levels stabilize hypoxia-inducible factor-1α by inhibiting prolyl hydroxylases, which enhances inflammatory responses. Notably, also acts extracellularly signaling molecule engaging receptor 1 on immune cells, thus modulating their pro-inflammatory or anti-inflammatory activities. Alterations have been associated with various disorders, including rheumatoid arthritis, bowel disease, obesity, atherosclerosis. These associations are primarily due exaggerated cell Given its central role inflammation, targeting pathways offers promising therapeutic avenues for these diseases. paper provides extensive review succinate's involvement processes highlights potential targets future research possibilities development.

Язык: Английский

Процитировано

25
Lactate enhances NMNAT1 lactylation to sustain nuclear NAD+ salvage pathway and promote survival of pancreatic adenocarcinoma cells under glucose-deprived conditions DOI
Huimin Huang, Shitong Wang, Hongping Xia

и другие.

Cancer Letters, Год журнала: 2024, Номер 588, С. 216806 - 216806

Опубликована: Март 11, 2024

Язык: Английский

Процитировано

22
Redox regulation: mechanisms, biology and therapeutic targets in diseases DOI Creative Commons
Bowen Li, Hui Ming, Siyuan Qin

и другие.

Signal Transduction and Targeted Therapy, Год журнала: 2025, Номер 10(1)

Опубликована: Март 7, 2025

Redox signaling acts as a critical mediator in the dynamic interactions between organisms and their external environment, profoundly influencing both onset progression of various diseases. Under physiological conditions, oxidative free radicals generated by mitochondrial respiratory chain, endoplasmic reticulum, NADPH oxidases can be effectively neutralized NRF2-mediated antioxidant responses. These responses elevate synthesis superoxide dismutase (SOD), catalase, well key molecules like nicotinamide adenine dinucleotide phosphate (NADPH) glutathione (GSH), thereby maintaining cellular redox homeostasis. Disruption this finely tuned equilibrium is closely linked to pathogenesis wide range Recent advances have broadened our understanding molecular mechanisms underpinning dysregulation, highlighting pivotal roles genomic instability, epigenetic modifications, protein degradation, metabolic reprogramming. findings provide foundation for exploring regulation mechanistic basis improving therapeutic strategies. While antioxidant-based therapies shown early promise conditions where stress plays primary pathological role, efficacy diseases characterized complex, multifactorial etiologies remains controversial. A deeper, context-specific signaling, particularly redox-sensitive proteins, designing targeted aimed at re-establishing balance. Emerging small molecule inhibitors that target specific cysteine residues proteins demonstrated promising preclinical outcomes, setting stage forthcoming clinical trials. In review, we summarize current intricate relationship disease also discuss how these insights leveraged optimize strategies practice.

Язык: Английский

Процитировано

11
HIF-1 and HIF-2 in cancer: structure, regulation, and therapeutic prospects DOI Creative Commons

Yi Shi,

Daniele M. Gilkes

Cellular and Molecular Life Sciences, Год журнала: 2025, Номер 82(1)

Опубликована: Янв. 18, 2025

Hypoxia, or a state of low tissue oxygenation, has been characterized as an important feature solid tumors that is related to aggressive phenotypes. The cellular response hypoxia controlled by Hypoxia-inducible factors (HIFs), family transcription factors. HIFs promote the gene products play role in tumor progression including proliferation, angiogenesis, metastasis, and drug resistance. HIF-1 HIF-2 are well known widely described. Although these proteins share high degree homology, have non-redundant roles cancer. In this review, we summarize similarities differences between HIF-1α HIF-2α their structure, expression, DNA binding. We also discuss canonical non-canonical regulation under hypoxic normal conditions. Finally, outline recent strategies aimed at targeting and/or HIF-2α.

Язык: Английский

Процитировано

7
Hypoxia-inducible factor and cellular senescence in pulmonary aging and disease DOI Creative Commons
Riya Thapa,

Arockia Babu Marianesan,

Arcot Rekha

и другие.

Biogerontology, Год журнала: 2025, Номер 26(2)

Опубликована: Фев. 26, 2025

Abstract Cellular senescence and hypoxia-inducible factor (HIF) signaling are crucial in pulmonary aging age-related lung diseases such as chronic obstructive disease idiopathic fibrosis cancer. HIF plays a pivotal role cellular adaptation to hypoxia, regulating processes like angiogenesis, metabolism, inflammation. Meanwhile, leads irreversible cell cycle arrest, triggering the senescence-associated secretory phenotype which contributes inflammation, tissue remodeling, fibrosis. Dysregulation of these pathways accelerates progression by promoting oxidative stress, mitochondrial dysfunction, epigenetic alterations. Recent studies indicate that interact at multiple levels, where can both induce suppress senescence, depending on conditions. While transient activation supports repair stress resistance, dysregulation exacerbates pathologies. Furthermore, emerging evidence suggests targeting could offer new therapeutic strategies mitigate diseases. This review explores intricate crosstalk between mechanisms, shedding light how their interplay influences progression. Additionally, we discuss potential interventions, including senolytic therapies modulators, enhance health longevity.

Язык: Английский

Процитировано

3