Mechanisms of drug resistance in nutrient-depleted colorectal cancer cells: insights into lysosomal and mitochondrial drug sequestration DOI Creative Commons
Shingo Kose, Aliye Ezgi Güleç Taşkıran

Biology Open, Journal Year: 2024, Volume and Issue: 13(10)

Published: July 15, 2024

ABSTRACT This Review delves into the mechanisms behind drug resistance in colorectal cancer (CRC), particularly examining role of nutrient depletion and its contribution to multidrug (MDR). The study highlights metabolic adaptations cells as well under low availability, including shifts glycolysis lipid metabolism. It emphasizes significance MDR1 encoded efflux transporter, P-glycoprotein (P-gp/B1), mediating how pathways such HIF1α, AKT, mTOR influence expression P-gp/B1 limited availability. Additionally, explores dual roles autophagy sensitivity conditions. further investigates involvement lysosomes mitochondria, focusing on their sequestration challenges posed by lysosomal entrapment facilitated non-enzymatic processes ABC transporters like P-gp/B1. Finally, underscores importance understanding interplay between sequestration, functions, depletion, gene modulation. suggests innovative strategies, structural modifications nanotechnology, promising approaches overcoming therapy.

Language: Английский

GPR176 Promotes Cancer Progression by Interacting with G Protein GNAS to Restrain Cell Mitophagy in Colorectal Cancer DOI Creative Commons
Junwei Tang, Wen Peng,

Jiangzhou Ji

et al.

Advanced Science, Journal Year: 2023, Volume and Issue: 10(12)

Published: March 11, 2023

Abstract GPR176 belongs to the G protein‐coupled receptor superfamily, which responds external stimuli and regulates cancer progression, but its role in colorectal (CRC) remains unclear. In present study, expression analyses of are performed patients with cancer. Genetic mouse models CRC coupled Gpr176‐deficiency investigated, vivo vitro treatments conducted. A positive correlation between upregulation proliferation poor overall survival is demonstrated. confirmed activate cAMP/PKA signaling pathway modulate mitophagy, promoting oncogenesis development. Mechanistically, protein GNAS recruited intracellularly transduce amplify extracellular signals from GPR176. homolog model tool that recruits via transmembrane helix 3‐intracellular loop 2 domain. The GPR176/GNAS complex inhibits mitophagy cAMP/PKA/BNIP3L axis, thereby tumorigenesis progression CRC.

Language: Английский

Citations

26
Targeting cellular mitophagy as a strategy for human cancers DOI Creative Commons
Yuming Dong, Xue Zhang

Frontiers in Cell and Developmental Biology, Journal Year: 2024, Volume and Issue: 12

Published: July 5, 2024

Mitophagy is the cellular process to selectively eliminate dysfunctional mitochondria, governing number and quality of mitochondria. Dysregulation mitophagy may lead accumulation damaged which plays an important role in initiation development tumors. includes ubiquitin-dependent pathways mediated by PINK1/Parkin non-ubiquitin dependent mitochondrial autophagic receptors including NIX, BNIP3, FUNDC1. Cellular widely participates multiple metabolic reprogramming, anti-tumor immunity, ferroptosis, as well interaction between tumor cells tumor-microenvironment. And also regulates proliferation metastasis, stemness, chemoresistance, resistance targeted therapy radiotherapy. In this review, we summarized underlying molecular mechanisms discussed complex diverse contexts tumors, indicating it a promising target mitophagy-related therapy.

Language: Английский

Citations

9
The dark sides of the GPCR tree ‐ research progress on understudied GPCRs DOI Creative Commons
Magdalena M. Scharf, Laura J. Humphrys, Sandra Berndt

et al.

British Journal of Pharmacology, Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 10, 2024

Abstract A large portion of the human GPCRome is still in dark and understudied, consisting even entire subfamilies GPCRs such as odorant receptors, class C orphans, adhesion GPCRs, Frizzleds taste receptors. However, it undeniable that these bring an untapped therapeutic potential should be explored further. Open questions on span diverse topics deorphanisation, development tool compounds tools for studying well understanding basic signalling mechanisms. This review gives overview current state knowledge each understudied receptors regarding their physiological relevance, molecular mechanisms, endogenous ligands pharmacological tools. Furthermore, identifies some largest gaps addressed foreseeable future lists general strategies might helpful this process.

Language: Английский

Citations

6
Exosomal miR‐1470 is a diagnostic biomarker and promotes cell proliferation and metastasis in colorectal cancer DOI Creative Commons
Yawen Wu, Jie Zhang,

Fanfeng Lin

et al.

Cancer Medicine, Journal Year: 2024, Volume and Issue: 13(7)

Published: March 28, 2024

Abstract Background In recent years,the lack of specific markers for the diagnosis colorectal cancer has led to an upward trend in both morbidity and mortality from this condition. There is urgent need identify molecular biomarkers that contribute early detection. This study aimed exosomal microRNAs hold potential as diagnostic CRC. Methods We screened differentially expressed miRNAs using CRC exosome dataset GSE39833. To validate results public database, we collected serum 168 patients healthy volunteers. The expression levels miR‐1470 volunteers were analyzed qRT‐PCR. evaluate selected distinguishing controls, its receiver operating characteristic curve. explore biological functions cell lines, detected miR‐1470's ability regulate growth metastasis cells by CCK8, transwell other assays after transfection SW480, HCT‐116 cells. Results Exosomal exhibited significant up‐regulation compared ROC curve analysis revealed area under (AUC) 0.74 (95% confidence interval: 0.6876–0.7920) miR‐1470, indicating a biomarker. Furthermore, level showed correlations with age, metastasis, HDL content. overexpressed lines. CCK8 proliferation assay promoted SW480 Transwell migration invasion Conclusion suggested non‐invasive possible detecting exosomes, which important implications detection treatment disease.

Language: Английский

Citations

5
An update on regulation and function of G protein-coupled receptors in cancer: A promising strategy for cancer therapy DOI
Lin Li,

Zihao An,

Chao Lin

et al.

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2025, Volume and Issue: unknown, P. 189266 - 189266

Published: Jan. 1, 2025

Language: Английский

Citations

0
The Use of Biologics for Targeting GPCRs in Metastatic Cancers DOI Creative Commons
Cian McBrien, David O’Connell

BioTech, Journal Year: 2025, Volume and Issue: 14(1), P. 7 - 7

Published: Jan. 30, 2025

A comprehensive review of studies describing the role G-protein coupled receptor (GPCR) behaviour contributing to metastasis in cancer, and developments biotherapeutic drugs towards targeting them, provides a valuable resource toward improving our understanding opportunities effectively target this malignant tumour cell adaptation. Focusing on five most common metastatic cancers lung, breast, colorectal, melanoma, prostate we highlight well-studied characterised GPCRs some less studied receptors that are also implicated development cancers. Of approximately 390 relevant therapeutic targeting, as many 125 these have been identified play promoting disease cancer types. GPCR signalling through well-characterised pathways chemokine receptors, emerging data by orphan is integral aspects phenotype. Despite having detailed information their ligands, there only thirteen approved therapeutics specifically for which three small molecules with remainder including synthetic non-synthetic peptides or monoclonal antibodies. This will cover existing potential use antibodies, proteins peptides, nanobodies therapy.

Language: Английский

Citations

0
Screening of Regulatory mRNAs and miRNAs that Suppress Staphylococcus aureus Proliferation via Macrophage Ferroptosis DOI
Lili Wang, Jiajia Bao,

Danyang Yang

et al.

Current Microbiology, Journal Year: 2025, Volume and Issue: 82(4)

Published: Feb. 11, 2025

Language: Английский

Citations

0
GPR176 enhances the epithelial-mesenchymal transition in gastric cancer cells by activating the PI3K/AKT/mTOR signaling pathway DOI Creative Commons

Guang-Chuan Mu,

Kaiyan Li, Chen Hu

et al.

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 17, 2025

Abstract Gastric cancer is characterized by a high incidence and unfavorable prognosis. The exploration of novel molecular markers deeper understanding their mechanisms action hold the potential to offer fresh insights into gastric treatment. Leveraging TCGA-STAD GSE66254 datasets, this study conducted an analysis on relationship between GPR176 clinical pathological features. Furthermore, it was validated in patients from First Affiliated Hospital Guangxi Medical University. Cell migration invasion capabilities were evaluated through Transwell scratch assays. Western blot performed detect impact PI3K/AKT/mTOR signaling pathway. Nude mouse tumorigenesis experiments validate tumor growth in vivo. exhibited higher expression levels tissues, associated with poor prognosis cancer. Significant downregulation suppressed invasive migratory cells, concomitant inhibition PI3K EMT pathways. However, phenotypic changes induced its inhibitory effects could be reversed overexpression PIP5K1A. findings cell experiments, demonstrating that growth, while promoted growth. Similarly, after downregulation, pathways cells significantly inhibited, whereas upregulation led substantial activation. In conclusion, emerged as newly identified prognostic marker study. may promote activating

Language: Английский

Citations

0
Contract to kill: GNAS mutation DOI Creative Commons

Pratima Raut,

Poompozhil Mathivanan,

Surinder K. Batra

et al.

Molecular Cancer, Journal Year: 2025, Volume and Issue: 24(1)

Published: March 7, 2025

The mutation in Gsα-coding GNAS exons, popular as gsp oncogene, is the most frequent across all heterotrimeric G proteins involved oncogenesis. R201, frequently mutated, followed by Q227, are found predominantly various neoplasms and cancers such IPMN, pituitary, thyroid, appendiceal, colorectal, etc. This review emphasizes pivotal significance of oncogene its ramifications underpinning sustained addiction to mutation. Recent studies delineating mechanistic intricacies that provide solid evidence profound impact oncogenic on tumor formation, progression, maintenance highlighted. We have leveraged discoveries Gsα an ideal neoantigen candidate for vaccine therapy, allele-specific inhibitors, cyclic peptide-based small molecular inhibitors explored therapeutic potential target directly. Alternative modalities patient-centric mitigate mutations also discussed. exposition novel strategies designed address challenges inherent these approaches targeting activating GNAS, along with probable avenues further investigation, aims reverberate current understanding genomic biological landscape GNAS-driven cancers, against them.

Language: Английский

Citations

0
SALL4/ABCB6 Axis Suppresses Ferroptosis in Colon Cancer by Mediating Mitophagy DOI Creative Commons
Leilei Yang,

Yuehuai Xu,

Jiaju Han

et al.

Journal of Biochemical and Molecular Toxicology, Journal Year: 2025, Volume and Issue: 39(3)

Published: March 1, 2025

According to reports, the inhibition of ferroptosis is an essential culprit malignant progression in various tumors, including colon cancer (CC). However, relevant study on regulatory mechanism CC sparse. This project was designed identify key genes modulating as well specific mechanisms. Based The Cancer Genome Atlas (TCGA)-CC mRNA expression data and immunohistochemistry assay, we analyzed ABCB6 SALL4 tissue. HTFtarget employed predict binding sites. cells by quantitative polymerase chain reaction, interaction between verified dual-luciferase chromatin immunoprecipitation experiments. Cell viability tested cell counting kit-8 colony formation assay. malondialdehyde (MDA), Fe2+ content, lipid reactive oxygen species (ROS) levels were examined utilizing corresponding reagent kits. protein ABCB6, SALL4, GPX4, GCLC, SLC3A2 determined via western blot. High detected CC. overexpression suppressed dramatically declined MDA, ROS, cells. Furthermore, it induced mitochondrial membrane potential dysfunction substantially fluorescence intensity GFP-LC3, which turn promoted proteins prevented ferroptosis. rescue experiment that initiated activation mediate mitophagy prevent findings evidenced SALL4/ABCB6 axis suppresses hinder pathway may be for regulate

Language: Английский

Citations

0