Emerging therapeutic strategies for Wnt-dependent colon cancer targeting macropinocytosis DOI Creative Commons
Nydia Tejeda‐Muñoz, Grace Binder, Kuo‐Ching Mei

et al.

Cells and Development, Journal Year: 2024, Volume and Issue: 180, P. 203974 - 203974

Published: Nov. 9, 2024

Aberrations in the Wnt signaling pathway, particularly mutations genes like APC and β-catenin, are pivotal initiating driving progression of colorectal cancer (CRC), establishing this pathway as a crucial target for therapeutic intervention. Membrane trafficking plays key role regulating by controlling activation, modulation, secretion essential molecules that contribute to CRC progression. This review explores connection between membrane signaling, with specific focus on macropinocytosis-an endocytic process involved nutrient uptake also signal regulation. The relationship macropinocytosis, critical both embryonic development onset, reveals new dimension Targeting through modulation macropinocytosis broader pathways presents promising strategy, several candidates already early clinical trials. These emerging approaches underscore potential targeting its associated processes treatment, aligning innovative therapies.

Language: Английский

Molecular Mechanisms of Synergistic Effect of PRIMA‐1met and Oxaliplatin in Colorectal Cancer With Different p53 Status DOI Creative Commons

X. Li,

Jianbiao Zhou, Nanyun Tang

et al.

Cancer Medicine, Journal Year: 2025, Volume and Issue: 14(1)

Published: Jan. 1, 2025

ABSTRACT Background The toxicity and drug resistance associated with oxaliplatin (L‐OHP) limit its long‐term use for colorectal cancer (CRC) patients. p53 mutation is a common genetic trait of CRC. PRIMA‐1 met (APR‐246, eprenetapopt) restores the DNA‐binding capacity different mutant P53 proteins. has progressed to Phase III clinical trial. Our study explores combination therapy L‐OHP CRC status. Methods Cell viability was assessed Counting Kit‐8 (CCK‐8) assay index (CI) calculated using Chou‐Talalay method. We also employed wound healing colony formation determine effect L‐OHP, their combination. Weighted gene co‐expression network analysis (WGCNA) RNA‐seq data conducted identify key modules central genes related treatment modalities. Xenograft mouse model used assess in vivo. Results findings showed heightened cytotoxicity inhibition migration, cells treated both drugs, irrespective status, presenting promising avenue addressing toxicity. revealed differential responses between p53‐wide type HCT116 p53‐mutant DLD‐1 cells, pathway alterations implicated tumorigenesis. WGCNA identified hub response. In vivo studies demonstrated enhanced efficacy combined over alone, while mitigating L‐OHP‐induced Conclusions summary, our research reveals molecular mechanisms wild p53. not only demonstrate that this regimen exerts synergistic anti‐CRC vitro vivo, but suggest benefit on prevention L‐OHP‐related side effects. These underscore potential ‐L‐OHP CRC, offering reduced toxicity, warranting further investigation.

Language: Английский

Citations

0
Folic acid-targeted β-lactoglobulin nanocarriers for enhanced delivery of 5-fluorouracil and sodium butyrate in colorectal cancer treatment DOI

Rosalinda Heydarian,

Adeleh Divsalar, Homa Mohseni Kouchesfahani

et al.

International Journal of Pharmaceutics, Journal Year: 2025, Volume and Issue: unknown, P. 125262 - 125262

Published: Jan. 1, 2025

Language: Английский

Citations

0
m6A-modified LINC02418 induces transcriptional and post-transcriptional modification of CTNNB1 via interacting with YBX1 and IGF2BP1 in colorectal cancer DOI Creative Commons
Hao Zhang, Ye Han, Chengwei Wu

et al.

Cell Death Discovery, Journal Year: 2025, Volume and Issue: 11(1)

Published: March 13, 2025

Abstract Colorectal cancer (CRC) represents a significant menace to human health, but its molecular pathogenesis remains unclear. Herein, we explored the functional role of LINC02418 in CRC progression. The function was determined through vitro and vivo experiments. mechanism by quantitative real-time PCR (qPCR) analyses, western blot, luciferase reporter assay, methylated RNA immunoprecipitation (MeRIP) pull-down, (RIP) assay chromatin (ChIP) assay. results revealed that expression upregulated tissues high related unfavorable survival patients. Besides, knockdown resulted inhibition proliferation metastasis cells vivo. Mechanistically, found METTL3-mediated m6A modification induced aberrant CRC. could interact with YBX1 enhance DNA-binding ability CTNNB1 promoter, resulting transcriptional activation CTNNB1. In post-transcriptional stage, also stability promoting interaction between IGF2BP1 protein mRNA. What is more, be transcriptionally enhanced protein. Collectively, this study unveils novel oncogenic for might therapeutic target treatment.

Language: Английский

Citations

0
Salidroside inhibits the invasion and migration of colorectal cancer cells by regulating MMP-12 and WNT signaling pathway DOI
Hong Ye, Yanrong Li, Xia Liu

et al.

American Journal of Cancer Research, Journal Year: 2025, Volume and Issue: 15(3), P. 929 - 945

Published: Jan. 1, 2025

Colorectal cancer (CRC) is a prevalent and highly lethal malignancy, with current therapeutic efficacy limited by the tumor's high invasiveness metastatic potential. Matrix metalloproteinases (MMPs) WNT (Wingless/Integrated) signaling pathway play key roles in invasion metastasis of CRC. Salidroside, natural compound, has demonstrated inhibitory effects several cancers, but its precise molecular mechanism CRC cells remains unclear. This study aims to investigate antitumor effect salidroside on influencing epithelial-mesenchymal transition (EMT) regulating MMP-12 pathway. The cell proliferation, migration, were evaluated through vitro experiments using HCT-116 SW620 lines. validated CCK-8, wound healing, Transwell assays. Expression changes MMP-12, signaling-related proteins (e.g., β-catenin, GSK-3β), EMT markers E-cadherin, Vimentin) after treatment measured qRT-PCR Western Blot. Additionally, bioinformatics analysis was performed TCGA GEO databases combination BEST online tool identify differentially expressed genes, followed GSEA enrichment analysis. Salidroside showed significant antiproliferative migration cells. In that significantly inhibited proliferation reduced their capabilities. Blot analyses downregulated expression led EMT-related proteins, specifically downregulating upregulating Vimentin. Furthermore, indicated plays crucial role salidroside-mediated inhibition, further supporting potential as target. conclusion, suppresses modulating pathway, thereby inhibiting process. These findings suggest holds agent for CRC, offering novel approach treatment.

Language: Английский

Citations

0
Low expression of OXCT1 promote colorectal cancer liver metastasis by upregulating CDK8 and β-catenin via H3 acetylation DOI Creative Commons
Chenhao Li,

Deao Gong,

Xiaoqun Shan

et al.

Genes & Diseases, Journal Year: 2025, Volume and Issue: unknown, P. 101625 - 101625

Published: April 1, 2025

Language: Английский

Citations

0
Na,K-ATPase activity promotes macropinocytosis in colon cancer via Wnt signaling DOI Creative Commons
Nydia Tejeda‐Muñoz, Yagmur Azbazdar, Eric Sosa

et al.

Biology Open, Journal Year: 2024, Volume and Issue: 13(5)

Published: May 7, 2024

ABSTRACT Recent research has shown that membrane trafficking plays an important role in canonical Wnt signaling through sequestration of the β-catenin destruction complex inside multivesicular bodies (MVBs) and lysosomes. In this study, we introduce Ouabain, inhibitor Na,K-ATPase pump establishes electric potentials across membranes, as a potent signaling. We find levels are elevated advanced colon carcinoma, enzyme is cancer cells with constitutively activated pathway by GSK3 inhibitors increase macropinocytosis. Ouabain blocks macropinocytosis, which essential step signaling, probably explaining strong effects on pathway. Xenopus embryos, brief treatment at 32-cell stage, critical for earliest signal development-inhibited brains, could be reversed Lithium chloride, mimic. Inhibiting may provide way targeting Wnt-driven cancers.

Language: Английский

Citations

2
miR‐27a‐3p regulates intestinal cell proliferation and differentiation through Wnt/β‐catenin signalling DOI Creative Commons
Chang Li, Yuning Zhou,

Yinping Jiang

et al.

Cell Proliferation, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 27, 2024

Abstract Intestinal stem cells differentiate into absorptive enterocytes, characterised by increased brush border enzymes such as intestinal alkaline phosphatase (IAP), making up the majority (95%) of terminally differentiated in villus. Loss integrity epithelium plays a key role inflammatory diseases and gastrointestinal infection. Here, we show that microRNA (miR)‐27a‐3p is an important regulator epithelial cell proliferation enterocyte differentiation. Repression endogenous miR‐27a‐3p leads to differentiation decreased mouse human small organoids. Mechanistically, regulates at least part through regulation retinoic acid receptor α (RXRα), modulator Wnt/β‐catenin signalling. increases expression RXRα concomitantly, decreases active β‐catenin cyclin D1. In contrast, overexpression mimic Moreover, results impaired proliferation. These alterations were attenuated or blocked Wnt inhibition. Our study demonstrates miR‐27a‐3p/RXRα/Wnt/β‐catenin pathway for maintenance homeostasis intestine.

Language: Английский

Citations

2
Interactions between genistein and Wnt pathway in colon adenocarcinoma and early embryos DOI Creative Commons
Yagmur Azbazdar, Eric Sosa,

Julia Monka

et al.

Heliyon, Journal Year: 2024, Volume and Issue: 10(11), P. e32243 - e32243

Published: June 1, 2024

Language: Английский

Citations

1
Wnt signaling in the tumor microenvironment: A driver of brain tumor dynamics DOI Creative Commons

Han Na Suh,

Gee Euhn Choi

Life Sciences, Journal Year: 2024, Volume and Issue: unknown, P. 123174 - 123174

Published: Oct. 1, 2024

Language: Английский

Citations

1
Emerging therapeutic strategies for Wnt-dependent colon cancer targeting macropinocytosis DOI Creative Commons
Nydia Tejeda‐Muñoz, Grace Binder, Kuo‐Ching Mei

et al.

Cells and Development, Journal Year: 2024, Volume and Issue: 180, P. 203974 - 203974

Published: Nov. 9, 2024

Aberrations in the Wnt signaling pathway, particularly mutations genes like APC and β-catenin, are pivotal initiating driving progression of colorectal cancer (CRC), establishing this pathway as a crucial target for therapeutic intervention. Membrane trafficking plays key role regulating by controlling activation, modulation, secretion essential molecules that contribute to CRC progression. This review explores connection between membrane signaling, with specific focus on macropinocytosis-an endocytic process involved nutrient uptake also signal regulation. The relationship macropinocytosis, critical both embryonic development onset, reveals new dimension Targeting through modulation macropinocytosis broader pathways presents promising strategy, several candidates already early clinical trials. These emerging approaches underscore potential targeting its associated processes treatment, aligning innovative therapies.

Language: Английский

Citations

1