Desmoglein 3 contributes to tumorigenicity of pancreatic ductal adenocarcinoma through activating Src–FAK signaling

Yimamumaimaitijiang, Abula; Su, Yating; Tuniyazi, Dilixiati; Yi, Chao

doi:10.1080/19768354.2021.1943707

Cited by 10 publications

(8 citation statements)

References 31 publications

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“…Notably, DSG3 emerged as another classifier among the analyzed molecules. These findings align with previous functional studies highlighting the significant role of DSG3 in tumor progression, particularly in differentiating adenocarcinoma (ADC) from squamous cell carcinoma (SCC) [48,49].…”

Section: Discussionsupporting

confidence: 91%

Six-Gene Signature for Differential Diagnosis and Therapeutic Decisions in Non-Small-Cell Lung Cancer—A Validation Study

Charkiewicz,

Sulewska,

Karabowicz

et al. 2024

IJMS

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Non-small-cell lung cancer (NSCLC) poses a challenge due to its heterogeneity, necessitating precise histopathological subtyping and prognostication for optimal treatment decision-making. Molecular markers emerge as a potential solution, overcoming the limitations of conventional methods and supporting the diagnostic–therapeutic interventions. In this study, we validated the expression of six genes (MIR205HG, KRT5, KRT6A, KRT6C, SERPINB5, and DSG3), previously identified within a 53-gene signature developed by our team, utilizing gene expression microarray technology. Real-time PCR on 140 thoroughly characterized early-stage NSCLC samples revealed substantial upregulation of all six genes in squamous cell carcinoma (SCC) compared to adenocarcinoma (ADC), regardless of clinical factors. The decision boundaries of the logistic regression model demonstrated effective separation of the relative expression levels between SCC and ADC for most genes, excluding KRT6C. Logistic regression and gradient boosting decision tree classifiers, incorporating all six validated genes, exhibited notable performance (AUC: 0.8930 and 0.8909, respectively) in distinguishing NSCLC subtypes. Nevertheless, our investigation revealed that the gene expression profiles failed to yield predictive value regarding the progression of early-stage NSCLC. Our molecular diagnostic models manifest the potential for an exhaustive molecular characterization of NSCLC, subsequently informing personalized treatment decisions and elevating the standards of clinical management and prognosis for patients.

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Section: Discussionsupporting

confidence: 91%

Six-Gene Signature for Differential Diagnosis and Therapeutic Decisions in Non-Small-Cell Lung Cancer—A Validation Study

Charkiewicz,

Sulewska,

Karabowicz

et al. 2024

IJMS

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“…In this study, overexpression of LAMC2 promoted the expression of proteins related to integrin β 1/FAK/Src/AKT molecules, and knockdown of LAMC2 inhibited the expression of proteins related to integrin β 1/FAK/Src/AKT molecules, which further proved that LAMC2 promoted cell proliferation and invasion through the integrin β 1/FAK/Src/AKT signaling pathway. This was similar to what Abula et al found in PDAC cells, where PDAC proliferation and invasion were promoted by activating the Src/FAK/AKT signaling pathway [ 44 ]. Furthermore, Guo et al found that Src/Fak, Akt, and Erk1/2 signaling regulate proliferation and migration of gastric cancer cells [ 45 ].…”

Section: Discussionsupporting

confidence: 89%

Overexpression of Laminin 5γ2 Chain Correlates with Tumor Cell Proliferation, Invasion, and Poor Prognosis in Laryngeal Squamous Cell Carcinoma

Yin

Zhang

et al. 2022

Journal of Oncology

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Objective. Laryngeal squamous cell carcinoma (LSCC) is a common malignant tumor. Laminin 5γ2 chain (LAMC2) was reported to be associated with tumorigenesis. This study explored the role of LAMC2 on LSCC progression by regulating the integrinβ1/FAK/Src/AKT pathway. Methods. The level of LAMC2 in 46 LSCC patients was detected by qRT-PCR and western blot. Then the relationship between LAMC2 expression and LSCC malignancy as well as prognosis was analyzed, and the effect of LAMC2 expression on LSCC patient survival was also analyzed using the Kaplan–Meier survival curves. Afterwards, the LSCC cells were transfected with LAMC2 overexpression and knockdown vectors, the effect of LAMC2 on LSCC cell viability, proliferation ability, cell cycle, cell migration, and invasion were detected by CCK-8, colony formation, flow cytometry, wound healing, and Transwell assays. The expression of EMT-related biomarkers and integrin β1/FAK/Src/AKT signaling-related proteins was detected by western blot. Moreover, the effect of LAMC2 on LSCC tumor growth was evaluated by in vivo xenograft experiments and western blot. Results. LAMC2 was expressed at high level in LSCC tissues and associated with poor prognosis. LAMC2 overexpression increased TU177 cell viability, proliferation ability, promoted cell cycle, cell migration, and invasion capacity. The expression of N-cadherin, vimentin, and integrinβ1/FAK/Src/AKT related proteins was increased, while the expression of E-cadherin protein was decreased. When the LAMC2 knockdown in AMC-HN-8 cells had opposite effects. Furthermore, shLAMC2 decreased tumor volume and the expression of LAMC2, Ki-67 and integrinβ1, but increased the expression of E-cadherin in LSCC tumor-bearing mice. Conclusion. The findings suggested that LAMC2 was overexpressed in LSCC and correlated with poor prognosis. LAMC2 knockdown inhibited LSCC progression by regulating the integrinβ1/FAK/Src/AKT signaling pathway. Therefore, LAMC2 could be a target for LSCC therapy.

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“…AREG, a recently discovered molecule, mediates EMT of PC via the EGFR/ERK/NF-κB signaling pathway, which promotes PC growth and metastasis 44 . DSG3 is involved in numerous cell biology functions (cell growth and differentiation) 45 , is considered a negative prognostic biomarker for resected PC 46 and promotes PC tumorigenicity through the activation of the Src-FAK signaling pathway 47 . This study found that DSG3 was associated with higher clinical staging in PDAC patients and that its high expression predicted a worse outcome in PDAC patients.…”

Section: Discussionmentioning

confidence: 99%

Integrated single-cell and bulk RNA sequencing in pancreatic cancer identifies disulfidptosis-associated molecular subtypes and prognostic signature

Wu,

Shang,

Ruan

et al. 2023

Sci Rep

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Pancreatic cancer (PC) is known for its high degree of heterogeneity and exceptionally adverse outcome. While disulfidptosis is the most recently identified form of cell death, the predictive and therapeutic value of disulfidptosis-related genes (DRGs) for PC remains unknown. RNA sequencing data with the follow-up information, were retrieved from the TCGA and ICGC databases. Consensus clustering analysis was conducted on patient data using R software. Subsequently, the LASSO regression analysis was conducted to create a prognostic signature for foreseeing the outcome of PC. Differences in relevant pathways, mutational landscape, and tumor immune microenvironment were compared between PC samples with different risk levels. Finally, we experimentally confirmed the impact of DSG3 on the invasion and migration abilities of PC cells. All twenty DRGs were found to be hyperexpressed in PC tissues, and fourteen of them significantly associated with PC survival. Using consensus clustering analysis based on these DRGs, four DRclusters were identified. Additionally, altogether 223 differential genes were evaluated between clusters, indicating potential biological differences between them. Four gene clusters (geneClusters) were recognized according to these genes, and a 10-gene prognostic signature was created. High-risk patients were found to be primarily enriched in signaling pathways related to the cell cycle and p53. Furthermore, the rate of mutations was markedly higher in high-risk patients, besides important variations were present in terms of immune microenvironment and chemotherapy sensitivity among patients with different risk levels. DSG3 could appreciably enhance the invasion and migration of PC cells. This work, based on disulfidoptosis-related genes (DRGs), holds the promise of classifying PC patients and predicting their prognosis, mutational landscape, immune microenvironment, and drug therapy. These insights could boost an improvement in a better comprehension of the role of DRGs in PC as well as provide new opportunities for prognostic prediction and more effective treatment strategies.

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Desmoglein 3 contributes to tumorigenicity of pancreatic ductal adenocarcinoma through activating Src–FAK signaling

Cited by 10 publications

References 31 publications

Six-Gene Signature for Differential Diagnosis and Therapeutic Decisions in Non-Small-Cell Lung Cancer—A Validation Study

Six-Gene Signature for Differential Diagnosis and Therapeutic Decisions in Non-Small-Cell Lung Cancer—A Validation Study

Overexpression of Laminin 5γ2 Chain Correlates with Tumor Cell Proliferation, Invasion, and Poor Prognosis in Laryngeal Squamous Cell Carcinoma

Integrated single-cell and bulk RNA sequencing in pancreatic cancer identifies disulfidptosis-associated molecular subtypes and prognostic signature

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