NF‐κB as a regulator of cancer metastasis and therapy response: A focus on epithelial–mesenchymal transition

Journal of Cellular Physiology, Journal Year: 2022, Volume and Issue: 237(7), P. 2770 - 2795

Published: May 13, 2022

Metastasis of tumor cells is a complex challenge and significantly diminishes the overall survival prognosis cancer patients. The epithelial-to-mesenchymal transition (EMT) well-known mechanism responsible for invasiveness cells. A number molecular pathways can regulate EMT in nuclear factor-kappaB (NF-κB) one them. translocation NF-κB p65 induce transcription several genes involved induction. present review describes interaction their association progression. Due to oncogenic role signaling, its activation enhances metastasis via This has been confirmed various cancers including brain, breast, lung gastric cancers, among others. ZEB1/2, transforming growth factor-β, Slug as inducers undergo upregulation by promote After induction driven NF-κB, significant decrease occurs E-cadherin levels, while N-cadherin vimentin levels an increase. noncoding RNAs potentially also function upstream mediators modulate NF-κB/EMT axis cancers. Moreover, mediating drug resistance Thus, suppressing sensitivity chemotherapeutic agents.

Language: Английский

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Tumor cell plasticity in targeted therapy-induced resistance: mechanisms and new strategies

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: March 11, 2023

Abstract Despite the success of targeted therapies in cancer treatment, therapy-induced resistance remains a major obstacle to complete cure. Tumor cells evade treatments and relapse via phenotypic switching driven by intrinsic or induced cell plasticity. Several reversible mechanisms have been proposed circumvent tumor plasticity, including epigenetic modifications, regulation transcription factors, activation suppression key signaling pathways, as well modification environment. Epithelial-to-mesenchymal transition, stem formation also serve roads towards Corresponding treatment strategies recently developed that either target plasticity-related employ combination treatments. In this review, we delineate plasticity its manipulation evasion from therapy. We discuss non-genetic drug-induced various types tumors provide insights into contribution acquired drug resistance. New therapeutic such inhibition reversal are presented. multitude clinical trials ongoing worldwide with intention improving outcomes. These advances direction for developing novel therapy regimens

Language: Английский

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Biological impact and therapeutic perspective of targeting PI3K/Akt signaling in hepatocellular carcinoma: Promises and Challenges

Pharmacological Research, Journal Year: 2022, Volume and Issue: 187, P. 106553 - 106553

Published: Nov. 16, 2022

Cancer progression results from activation of various signaling networks. Among these, PI3K/Akt contributes to proliferation, invasion, and inhibition apoptosis. Hepatocellular carcinoma (HCC) is a primary liver cancer with high incidence rate, especially in regions prevalence viral hepatitis infection. Autoimmune disorders, diabetes mellitus, obesity, alcohol consumption, inflammation can also lead initiation development HCC. The treatment HCC depends on the identification oncogenic factors that tumor cells develop resistance therapy. present review article focuses role progression. Activation promotes glucose uptake, favors glycolysis increases cell proliferation. It inhibits both apoptosis autophagy while promoting survival. stimulates epithelial-to-mesenchymal transition (EMT) matrix-metalloproteinase (MMP) expression during metastasis. In addition increasing colony formation capacity facilitating spread cells, angiogenesis. Therefore, silencing prevents aggressive behavior. confer drug resistance, particularly sorafenib, decreases radio-sensitivity cells. Anti-cancer agents, like phytochemicals small molecules suppress by limiting Being upregulated tissues clinical samples, be used as biomarker predict patients' response

Language: Английский

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Noncoding RNAs as regulators of STAT3 pathway in gastrointestinal cancers: Roles in cancer progression and therapeutic response

Medicinal Research Reviews, Journal Year: 2023, Volume and Issue: 43(5), P. 1263 - 1321

Published: March 23, 2023

Abstract Gastrointestinal (GI) tumors (cancers of the esophagus, gastric, liver, pancreas, colon, and rectum) contribute to a large number deaths worldwide. STAT3 is an oncogenic transcription factor that promotes genes associated with proliferation, antiapoptosis, survival, metastasis. overactivated in many human malignancies including GI which accelerates tumor progression, metastasis, drug resistance. Research recent years demonstrated noncoding RNAs (ncRNAs) play major role regulation signaling pathways pathway. The types endogenous ncRNAs are being extensively studied oncology microRNAs, long RNAs, circular RNAs. These can either be tumor‐promoters or tumor‐suppressors each one them imparts their activity via different mechanisms. pathway also tightly modulated by ncRNAs. In this article, we have elaborated on tumor‐promoting tumors. Subsequently, comprehensively discussed as well suppressor functions mechanism action known modulate cancers.

Language: Английский

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Hepatocellular carcinoma: signaling pathways, targeted therapy, and immunotherapy

MedComm, Journal Year: 2024, Volume and Issue: 5(2)

Published: Feb. 1, 2024

Abstract Hepatocellular carcinoma (HCC) is the most common primary liver cancer with a high mortality rate. It regarded as significant public health issue because of its complicated pathophysiology, metastasis, and recurrence rates. There are no obvious symptoms in early stage HCC, which often leads to delays diagnosis. Traditional treatment methods such surgical resection, radiotherapy, chemotherapy, interventional therapies have limited therapeutic effects for HCC patients or metastasis. With development molecular biology immunology, signaling pathways immune checkpoint were identified main mechanism progression. Targeting these molecules has become new direction HCC. At present, combination targeted drugs inhibitors first choice advanced patients. In this review, we mainly focus on cutting‐edge research corresponding therapy immunotherapy great significance comprehensively understand pathogenesis search potential targets, optimize strategies

Language: Английский

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Natural medicinal compounds target signal transduction pathways to overcome ABC drug efflux transporter-mediated multidrug resistance in cancer

Drug Resistance Updates, Journal Year: 2023, Volume and Issue: 71, P. 101004 - 101004

Published: Aug. 21, 2023

Language: Английский

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Cellular and Molecular Biology of Cancer Stem Cells of Hepatocellular Carcinoma

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(2), P. 1417 - 1417

Published: Jan. 11, 2023

Hepatocellular carcinoma (HCC) is one of the leading causes cancer death globally. The stem cells (CSCs) HCC are responsible for tumor growth, invasion, metastasis, recurrence, chemoresistance, target therapy resistance and radioresistance. reported main surface markers used to identify liver CSCs include epithelial cell adhesion/activating molecule (EpCAM), cluster differentiation 90 (CD90), CD44 CD133. molecular signaling pathways Wnt/β-catenin, transforming growth factors-β (TGF-β), sonic hedgehog (SHH), PI3K/Akt/mTOR Notch. Patients with EpCAM-positive alpha-fetoprotein (AFP)-positive usually young but have advanced tumor-node-metastasis (TNM) stages. CD90-positive HCCs poorly differentiated worse prognosis. Those CD44-positive develop early metastases. CD133 expression a higher recurrence rate shorter overall survival. Wnt/β-catenin pathway triggers angiogenesis, infiltration metastasis through enhancement angiogenic factors. All CD133+ CSCs, CD133+/EpCAM+ CD44+ contribute sorafenib resistance. SHH could protect against ionizing radiation in an autocrine manner. Reducing CSC population crucial improvement HCC. However, targeting still challenging.

Language: Английский

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Targeting and regulation of autophagy in hepatocellular carcinoma: revisiting the molecular interactions and mechanisms for new therapy approaches

Cell Communication and Signaling, Journal Year: 2023, Volume and Issue: 21(1)

Published: Feb. 9, 2023

Autophagy is an evolutionarily conserved process that plays a role in regulating homeostasis under physiological conditions. However, dysregulation of autophagy observed the development human diseases, especially cancer. has reciprocal functions cancer and may be responsible for either survival or death. Hepatocellular carcinoma (HCC) one most lethal common malignancies liver, smoking, infection, alcohol consumption can lead to its development. Genetic mutations alterations molecular processes exacerbate progression HCC. The function HCC controversial both tumor suppressive promoting. Activation affect apoptosis regulator proliferation glucose metabolism. Induction promote metastasis via induction EMT. In addition, stem cell formation HCC, pro-survival leads resistance chemotherapy radiotherapy. Targeting impairs growth improves response therapy. Of note, large number signaling pathways such as STAT3, Wnt, miRNAs, lncRNAs, circRNAs regulate Moreover, regulation (induction inhibition) by antitumor agents could suggested effective treatment this paper, we comprehensively review mechanisms discuss potential benefit targeting Video Abstract.

Language: Английский

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Wnt/β-Catenin Signaling and Resistance to Immune Checkpoint Inhibitors: From Non-Small-Cell Lung Cancer to Other Cancers

Biomedicines, Journal Year: 2023, Volume and Issue: 11(1), P. 190 - 190

Published: Jan. 12, 2023

Lung cancer is the leading cause of cancer-related deaths worldwide. The standard care for advanced non-small-cell lung (NSCLC) without driver-gene mutations a combination an anti-PD-1/PD-L1 antibody and chemotherapy, or anti-CTLA-4 with chemotherapy. Although there were fewer cases disease progression in early stages treatment than antibodies alone, only approximately half patients had long-term response. Therefore, it necessary to elucidate mechanisms resistance immune checkpoint inhibitors. Recent reports such include reduced cancer-cell immunogenicity, loss major histocompatibility complex, dysfunctional tumor-intrinsic interferon-γ signaling, oncogenic signaling immunoediting. Among these, Wnt/β-catenin pathway notable potential mechanism escape In this review, we will summarize findings on these NSCLC other cancers, focusing signaling. First, review molecular biology then discuss how can induce immunoediting We also describe various immune-checkpoint-inhibitor resistance. Finally, propose therapeutic approaches overcome mechanisms.

Language: Английский

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The role of N-glycosylation modification in the pathogenesis of liver cancer

Cell Death and Disease, Journal Year: 2023, Volume and Issue: 14(3)

Published: March 29, 2023

Abstract N-glycosylation is one of the most common types protein modifications and it plays a vital role in normal physiological processes. However, aberrant N-glycan are closely associated with pathogenesis diverse diseases, including processes such as malignant transformation tumor progression. It known that conformation glycoproteins altered during different stages hepatocarcinogenesis. Characterizing heterogeneity biological functions glycans liver cancer patients will facilitate deeper understanding molecular mechanisms injury In this article, we review hepatocarcinogenesis, focusing on epithelial-mesenchymal transition, extracellular matrix changes, microenvironment formation. We highlight its potential applications treatment or diagnosis cancer.

Language: Английский

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