Alcohol promotes epithelial mesenchymal transformation-mediated premetastatic niche formation of colorectal cancer by activating interaction between laminin-γ2 and integrin-β1

Nong, Feifei; Liang, Yuqi; Xing, Shangping; Xiao, Yin-Fang; Chen, Huihui; Wen, Bangchun

doi:10.3748/wjg.v28.i35.5154

Cited by 6 publications

(4 citation statements)

References 58 publications

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“…Laminin 332 and 411 promote Epithelial to Mesenchymal Transition Marker in 2D and 3D Colon Cancer (42). Alcohol promotes EMT-mediated premetastatic niche formation of colorectal cancer via interaction between laminin-γ2 (43). All in all, LAMB overexpression and macrophages, monocytes, CD4_ The enrichment of T and CD cells was positively correlated, and in most tumor types, the expression of LAMBs was signi cantly positively correlated with the in ltration level of TAM, especially M2 like TAM, which could inhibit tumor progression.…”

Section: Discussionmentioning

confidence: 99%

Integrative analysis the characterization of LAMBs in predicting the prognosis and the immunotherapy response of cancers

Tao

Yuan

Shi

et al. 2022

Preprint

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Background: Laminin subunit betas (LAMBs) are the major noncollagenous constituent of basement membranes that implicated in biological functions such as cell adhesion, metastasis. However, few studies have systematically analyzed the prognostic value and immune characteristics of LAMBs in pan-cancer types. Methods: A pan-cancer comprehensive analysis of LAMBs in expression levels, protein localization, structure, mutations and methylation were explored. Next, Cox regression and Kaplan-Meier method were applied to analyze the prognostic role of LAMBs in pan-cancer. Protein-Protein Interaction (PPI) analysis was performed in the GeneMANIA database, and enrichment analysis was predicted signaling pathways were identifified by using Gene Ontology (GO), Kyoto Encyclopedia of Genes (KEGG) and gene set variation analysis (GSVA) analysis. The immune characteristics of LAMBs in the tumor microenvironment were evaluated via ImmuCellAI and TIMER 2.0. was the main platform to investigate the tumor associated macrophages (TAMs) related to LAMBs in pan-cancer, especially M2-like TAMs. In addition, single-cell sequencing analysis and tracking tumor immunophenotype (TIP) were also conducted to validate the interaction immune role of LAMBs with macrophages in cancers. Furthermore, the immunoregulators, tumour mutational burden (TMB) and microsatellite instability (MSI) was performed to evaluate the immune response role of LAMBs in cancers. Finally, the immunotherapy response and drug sensitive small molecule drugs based on LAMBs expression were predicted. Results: The expression, mutation and methylation of LAMBs was aberrantly expressed in most cancer types and exhibited prognosis predictive ability in various cancers. In addition, our results also showed that LAMBs was signifificantly correlated with immune-activated (including pathways and biological processes), immune cell infifiltrations, immunoregulator expressions, TMB and MSI. Importantly, analysis of an independent immunotherapy cohorts revealed that low-risk patients had better immunotherapy responses and prognosis than high-risk patients in some cancers. Furthermore, the immunotherapy response and sensitive small molecule drugs which correlate with LAMBs expression in different cancer types, had a potent capability to predict immunotherapy response in pan-cancers. Conclusions: LAMBs expression may contribute to increased infiltration of TAMs, which not only acted as a potent prognostic factor to predict the clinical outcomes of cancer patients but was also a promising immunotherapy predictive biomarker for cancer patients treated with immune-checkpoint inhibitors (ICIs).

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Section: Discussionmentioning

confidence: 99%

Integrative analysis the characterization of LAMBs in predicting the prognosis and the immunotherapy response of cancers

Tao

Yuan

Shi

et al. 2022

Preprint

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“…As a result, PFK inhibition increased glycolysis and upregulated HIF1α, promoting the reprogramming of stem cell transcription factors and aided tumor growth in patients [92]. In addition, alcohol encourages the interaction between LAMC2 and ITGB1, increasing p-FAK/FAK, snail, fibronectin, N-cadherin, and SATB1 while decreasing E-cadherin in the alcohol group compared to the non-alcohol group [93]. It suggests that alcohol may encourage CRC metastasis by molecular processes that change the pre-metastatic environment [93].…”

Section: Itgb1 Involvement In Ecm Remodelingmentioning

confidence: 99%

“…In addition, alcohol encourages the interaction between LAMC2 and ITGB1, increasing p-FAK/FAK, snail, fibronectin, N-cadherin, and SATB1 while decreasing E-cadherin in the alcohol group compared to the non-alcohol group [93]. It suggests that alcohol may encourage CRC metastasis by molecular processes that change the pre-metastatic environment [93]. In PDAC, activation of pancreatic stellate cells (PSCs) is a feature.…”

Section: Itgb1 Involvement In Ecm Remodelingmentioning

confidence: 99%

Integrinβ-1 in disorders and cancers: molecular mechanisms and therapeutic targets

Su,

Mo,

Dong

et al. 2024

Cell Commun Signal

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Integrinβ-1 (ITGB1) is a crucial member of the transmembrane glycoprotein signaling receptor family and is also central to the integrin family. It forms heterodimers with other ligands, participates in intracellular signaling and controls a variety of cellular processes, such as angiogenesis and the growth of neurons; because of its role in bidirectional signaling regulation both inside and outside the membrane, ITGB1 must interact with a multitude of substances, so a variety of interfering factors can affect ITGB1 and lead to changes in its function. Over the past 20 years, many studies have confirmed a clear causal relationship between ITGB1 dysregulation and cancer development and progression in a wide range of benign diseases and solid tumor types, which may imply that ITGB1 is a prognostic biomarker and a therapeutic target for cancer treatment that warrants further investigation. This review summarizes the biological roles of ITGB1 in benign diseases and cancers, and compiles the current status of ITGB1 function and therapy in various aspects of tumorigenesis and progression. Finally, future research directions and application prospects of ITGB1 are suggested.

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“…Data from in vitro cell culture studies and experimental models revealed that ethanol elevates epithelial mesenchymal transformation in CRC by activating laminin subunit gamma-2 and integrin beta 1 signals. 105 Ethanol and/or acetaldehyde mediates activation of transforming growth factor-beta/Runt-related transcription factor 3/ Snail axis and glycogen synthase kinase-3 beta/β-catenin/ monocyte chemoattractant protein 1 pathway, subsequently promotes aggressiveness of CRC. 106 107 Chronic alcohol intake promotes metastasis of CRC via the chemokine (C-C motif) ligand 5/AMP-activated protein kinase pathway-induced autophagy.…”

Section: Alcohol-associated Colon Cancermentioning

confidence: 99%

Alcohol-associated bowel disease: new insights into pathogenesis

Maccioni,

Fu,

Horsmans

et al. 2023

egastro

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Excessive alcohol drinking can cause pathological changes including carcinogenesis in the digestive tract from mouth to large intestine, but the underlying mechanisms are not fully understood. In this review, we discuss the effects of alcohol on small and large intestinal functions, such as leaky gut, dysbiosis and alterations of intestinal epithelium and gut immune dysfunctions, commonly referred to as alcohol-associated bowel disease (ABD). To date, detailed mechanistic insights into ABD are lacking. Accumulating evidence suggests a pathogenic role of ethanol metabolism in dysfunctions of the intestinal tract. Ethanol metabolism generates acetaldehyde and acetate, which could potentially promote functional disruptions of microbial and host components of the intestinal barrier along the gastrointestinal tract. The potential involvement of acetaldehyde and acetate in the pathogenesis of the underlying ABD, including cancer, is discussed. We also highlight some gaps in knowledge existing in the field of ABD. Finally, we discuss future directions in exploring the role of acetaldehyde and acetate generated during chronic alcohol intake in various pathologies affecting different sites of the intestinal tract.

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Alcohol promotes epithelial mesenchymal transformation-mediated premetastatic niche formation of colorectal cancer by activating interaction between laminin-γ2 and integrin-β1

Cited by 6 publications

References 58 publications

Integrative analysis the characterization of LAMBs in predicting the prognosis and the immunotherapy response of cancers

Integrative analysis the characterization of LAMBs in predicting the prognosis and the immunotherapy response of cancers

Integrinβ-1 in disorders and cancers: molecular mechanisms and therapeutic targets

Alcohol-associated bowel disease: new insights into pathogenesis

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