Transcriptional regulation of EMT transcription factors in cancer

Seminars in Cancer Biology, Год журнала: 2023, Номер 97, С. 21 - 29

Опубликована: Окт. 5, 2023

Язык: Английский

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TMEM25 inhibits monomeric EGFR-mediated STAT3 activation in basal state to suppress triple-negative breast cancer progression

Nature Communications, Год журнала: 2023, Номер 14(1)

Опубликована: Апрель 24, 2023

Triple-negative breast cancer (TNBC) is a subtype of with poor outcome and lacks approved targeted therapy. Overexpression epidermal growth factor receptor (EGFR) found in more than 50% TNBC suggested as driving force progression TNBC; however, targeting EGFR using antibodies to prevent its dimerization activation shows no significant benefits for patients. Here we report that monomer may activate signal transducer activator transcription-3 (STAT3) the absence transmembrane protein TMEM25, whose expression frequently decreased human TNBC. Deficiency TMEM25 allows phosphorylate STAT3 independent ligand binding, thus enhances basal promote female mice. Moreover, supplying by adeno-associated virus strongly suppresses progression. Hence, our study reveals role monomeric-EGFR/STAT3 signaling pathway points out potential therapy

Язык: Английский

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STAT3 signaling in prostate cancer progression and therapy resistance: An oncogenic pathway with diverse functions

Biomedicine & Pharmacotherapy, Год журнала: 2023, Номер 158, С. 114168 - 114168

Опубликована: Янв. 3, 2023

The categorization of cancers demonstrates that prostate cancer is the most common malignancy in men and it causes high death annually. Prostate patients are diagnosed mainly via biomarkers such as PSA test show poor prognosis. cells rapidly diffuse into different parts body their metastasis also a reason for death. Current therapies include chemotherapy, surgery radiotherapy well targeted therapy. progression regulated by factors STAT3 signaling among them. Growth cytokines IL-6 can induce shows carcinogenic impact. Activation occurs promotes malignant behavior tumor cells. Induction increases glycolysis proliferation prevents apoptosis. Furthermore, induces EMT mechanism increasing metastasis. stimulates drug resistance limitation current works lack experiment related to role radio-resistance tumor. Calcitriol, capsazepine β-elemonic compounds capable targeting its inhibition In addition natural products, small molecules have been developed

Язык: Английский

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EZH2 in hepatocellular carcinoma: progression, immunity, and potential targeting therapies

Experimental Hematology and Oncology, Год журнала: 2023, Номер 12(1)

Опубликована: Июнь 2, 2023

Abstract Hepatocellular carcinoma (HCC) is the leading cause of cancer-related death. The accumulation genetic and epigenetic changes closely related to occurrence development HCC. Enhancer zeste homolog 2 (EZH2, a histone methyltransferase) suggested be one principal factors that mediates oncogenesis by acting as driver alternation. Recent studies show EZH2 widely involved in proliferation metastasis HCC cells. In this review, functions progression, role tumor immunity application EZH2-related inhibitors therapy are summarized.

Язык: Английский

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Disheveled3 enhanced EMT and cancer stem-like cells properties via Wnt/β-catenin/c-Myc/SOX2 pathway in colorectal cancer

Journal of Translational Medicine, Год журнала: 2023, Номер 21(1)

Опубликована: Май 5, 2023

Epithelial-to-mesenchymal transition (EMT) and cancer stem-like cells (CSLCs) play crucial role in tumor metastasis drug-resistance. Disheveled3 (DVL3) is involved malignant behaviors of cancer. However, the potential mechanism DVL3 remain elusive EMT CSLCs colorectal (CRC).

Язык: Английский

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PRMT6 methylation of STAT3 regulates tumor metastasis in breast cancer

Cell Death and Disease, Год журнала: 2023, Номер 14(10)

Опубликована: Окт. 9, 2023

Overcoming distant metastasis stands as a paramount challenge in enhancing the outcomes of breast cancer treatments. Thus, delving deeper into comprehending intricate mechanisms underlying becomes imperative, offering potential avenues for pioneering therapeutic approaches. PRMT6, an arginine N-methyltransferase, possesses ability to methylate both histone and non-histone proteins. It has been reported that methylation proteins impacts their cellular localization, stability, activation, consequently influencing tumor progression. However, extent which PRMT6-mediated protein influences cell metastasis, particularly context cancer, remains elusive. In this study, we established PRMT6 exerted positive regulatory influence on through vivo vitro experiments. Mechanistically, innovatively revealed asymmetrically di-methylated STAT3 at 729 (STAT3 R729me2a). This modification proved indispensable STAT3's membrane its interaction with JAK2, Y705 phosphorylation, PRMT6-driven metastasis. From clinical perspective, unearthed promising R729me2a robust prognostic marker predicting overall survival time patients. terms intervention, demonstrated significant capability inhibitor, EPZ020411, curtail vitro. sum, our study unveils pivotal biological role underscores prospective utility inhibitors effective strategies against STAT3-driven metastatic cancer.

Язык: Английский

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Chemotherapy-induced metastasis: molecular mechanisms and clinical therapies

Acta Pharmacologica Sinica, Год журнала: 2023, Номер 44(9), С. 1725 - 1736

Опубликована: Май 11, 2023

Язык: Английский

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Dual inhibition of MYC and SLC39A10 by a novel natural product STAT3 inhibitor derived from Chaetomium globosum suppresses tumor growth and metastasis in gastric cancer

Pharmacological Research, Год журнала: 2023, Номер 189, С. 106703 - 106703

Опубликована: Фев. 17, 2023

Gastric cancer remains one of the most common deadly diseases and lacks effective targeted therapies. In present study, we confirmed that signal transducer activator transcription 3 (STAT3) is highly expressed associated with a poor prognosis in gastric cancer. We further identified novel natural product inhibitor STAT3, termed XYA-2, which interacts specifically SH2 domain STAT3 (Kd = 3.29 μM) inhibits IL-6-induced phosphorylation at Tyr705 nuclear translocation. XYA-2 inhibited viability seven human cell lines 72-h IC50 values ranging from 0.5 to 0.7 μΜ. 1 μΜ colony formation migration ability MGC803 (72.6% 67.6%, respectively) MKN28 (78.5% 96.6%, cells. vivo studies, intraperitoneal administration (10 mg/kg/day, 7 days/week) significantly suppressed 59.8% 88.8% tumor growth MKN28-derived xenograft mouse model MGC803-derived orthotopic model, respectively. Similar results were obtained patient-derived (PDX) model. Moreover, treatment extended survival mice bearing PDX tumors. The molecular mechanism studies based on transcriptomics proteomics analyses indicated might exert its anticancer activity by synergistically inhibiting expression MYC SLC39A10, two downstream genes vitro vivo. Together, these findings suggested may be potent for treating cancer, dual inhibition SLC39A10 an therapeutic strategy STAT3-activated

Язык: Английский

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NETosis: Sculpting tumor metastasis and immunotherapy

Immunological Reviews, Год журнала: 2023, Номер 321(1), С. 263 - 279

Опубликована: Сен. 15, 2023

Summary The process of neutrophil extracellular traps (NETs) formation, called NETosis, is a peculiar death modality neutrophils, which was first observed as an immune response against bacterial infection. However, recent work has revealed the unique biology NETosis in facilitating tumor metastatic process. Neutrophil released by microenvironment (TME) shield cells from cytotoxic immunity, leading to impaired clearance. Besides, tapped NETs enable travel through vessels and subsequently seed distant organs. Targeted ablation been proven be beneficial potentiating efficacy cancer immunotherapy settings. This review outlines impact at almost all stages metastasis. Furthermore, understanding multifaceted interplay between TME components crucial for supporting rational development highly effective combination immunotherapeutic strategies with anti‐NETosis patients disease.

Язык: Английский

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In Situ Hydrogel Modulates cDC1‐Based Antigen Presentation and Cancer Stemness to Enhance Cancer Vaccine Efficiency

Advanced Science, Год журнала: 2024, Номер 11(20)

Опубликована: Апрель 2, 2024

Abstract Effective presentation of antigens by dendritic cells (DC) is essential for achieving a robust cytotoxic T lymphocytes (CTLs) response, in which cDC1 the key DC subtype high‐performance activation CTLs. However, low proportion, complex process, and high cost severely hindered generation application. Herein, study proposes an situ recruitment strategy with simultaneous inhibiting cancer stemness inducing CTL responses enhancing anti‐tumor effect. Fms‐like tyrosine kinase 3 ligand (FLT3L), Poly I:C, Nap‐CUM (NCUM), playing role recruitment, activation, antigen release decreasing tumor cell stemness, respectively, are co‐encapsulated hydrogel vaccine (FP/NCUM‐Gel). FP/NCUM‐Gel gelated after intra‐tumoral injection. With near‐infrared irradiation, immunogenic death occurred, signals released situ. recruited to tissue activated cross‐presentation, followed migrating lymph nodes activating Furthermore, inhibited napabucasin, can help CTLs achieve comprehensive killing. Collectively, proposed combined inhibition provides great immune response potential, providing new ideas clinical design.

Язык: Английский

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