The crucial role of CEMIP in cancer metastasis: Mechanistic insights and clinical implications

The FASEB Journal, Год журнала: 2025, Номер 39(1)

Опубликована: Янв. 6, 2025

Cancer metastasis is the leading cause of cancer-related deaths, making early detection and prevention metastatic progression critical research priorities. Recent studies have expanded our understanding CEMIP (KIAA1199, HYBID), revealing its involvement in cancer potential role slowing progression. plays roles several stages metastasis: First, promotes cell proliferation to maintain heterogeneity before process. Second, it facilitates detachment by promoting epithelial-mesenchymal transition (EMT) through alterations signaling pathways. Third, contributes adherence attachment enabling cells withstand death (anoikis ferroptosis) hypoxia. Fourth, during invasion process, induces hyaluronan depolymerization further modulates promote EMT. Lastly, pre-metastatic niche, influences tumor microenvironment hypoxia, angiogenesis, pathway changes, degradation. focused on leveraging as a diagnostic tool or predictor and/or targeting overcome resistance This review aims explore at each stage highlight recent advances inhibit

Язык: Английский

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Epithelial–mesenchymal plasticity in cancer: signaling pathways and therapeutic targets

MedComm, Год журнала: 2024, Номер 5(8)

Опубликована: Авг. 1, 2024

Abstract Currently, cancer is still a leading cause of human death globally. Tumor deterioration comprises multiple events including metastasis, therapeutic resistance and immune evasion, all which are tightly related to the phenotypic plasticity especially epithelial–mesenchymal (EMP). cells with EMP manifest in three states as transition (EMT), partial EMT, mesenchymal–epithelial transition, orchestrate switch heterogeneity tumor via transcriptional regulation series signaling pathways, transforming growth factor‐β, Wnt/β‐catenin, Notch. However, due complicated nature EMP, diverse process not fully understood. In this review, we systematically conclude biological background, regulating mechanisms well role therapy response. We also summarize range small molecule inhibitors, immune‐related approaches, combination therapies that have been developed target for outstanding EMP‐driven deterioration. Additionally, explore potential technique EMP‐based mechanistic investigation research, may burst vigorous prospects. Overall, elucidate multifaceted aspects progression suggest promising direction treatment based on targeting EMP.

Язык: Английский

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Cis‐Regulation of an m⁶A Eraser by an Insertion Variant Associated with Survival of Patients With Non‐Small Cell Lung Carcinoma

Advanced Science, Год журнала: 2024, Номер unknown

Опубликована: Дек. 16, 2024

Abstract N6‐methyladenosine (m 6 A) serves as one of the crucial RNA modifications for genes involved in cancer progression. Here, 7273 expression quantitative trait loci potentially regulating 30 m6A pathway are identified from GTEx database, with 69 single nucleotide polymorphisms significantly associated survival non‐small cell lung carcinoma (NSCLC) patients ( n = 1523) ongoing genome‐wide association study after false positive probability tests. Notably, rs151198415 locus, situated a potential enhancer region, demonstrated prolonged effect C>CCACG insertion, which is validated an independent prospective cohort 237), yielding pooled hazard ratio 0.72 p 0.007). Mechanistically, insertion engaged long‐range interaction promoter m A eraser ALKBH5 , promoting transcription by creation EGR1 binding site. Then, upregulated FBXL5 demethylation, dependent on H204 amino acid site and specific sites mRNA. Finally, ALKBH5‐FBXL5 axis reduces intracellular reactive oxygen species levels, leading to PI3K/AKT NF‐kB inhibition consequently suppresses NSCLC proliferation metastasis vitro vivo. Triggered variant, this remote cis‐regulation downstream molecular events modulate patients.

Язык: Английский

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POU4F1 enhances lung cancer gemcitabine resistance by regulating METTL3-dependent TWF1 mRNA N6 adenosine methylation

3 Biotech, Год журнала: 2024, Номер 15(1)

Опубликована: Дек. 12, 2024

Язык: Английский

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