Understanding the cell survival mechanism of anoikis-resistant cancer cells during different steps of metastasis

Khan, Sameer Ullah; Fatima, Kaneez; Malik, Fayaz

doi:10.1007/s10585-022-10172-9

Cited by 78 publications

(44 citation statements)

References 109 publications

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“…Anoikis is a special type of programmed cell death that plays a critical role in normal morphogenesis, tissue homeostasis, disease development, and tumor metastasis. When cells lose their attachment to ECM, the pro apoptotic protein Bmf, which remains on the cytoskeleton, dissociates from dynein light chain 2 and translocates to mitochondria, thus promoting the occurrence of nesting apoptosis ( 24 ). However, a common feature of tumor development and growth is the viability of transformed cells under “independent” growth conditions.…”

Section: Discussionmentioning

confidence: 99%

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Bioinformatics based exploration of hsa-miR-194-5p regulation of CHD4 through PI3K/AKT signal pathway to enhance tumor resistance to apoptosis due to loss of nests and participate in poor prognosis of oral squamous cell carcinoma

Li¹,

Wang²,

Shen³

et al. 2023

Ann Transl Med

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Background Recent evidence shows that CHD4 is involved in a variety of biological events of tumors. Our aim was to investigate the correlation between CHD4 and oral squamous cell carcinoma (OSCC). Methods After CHD4 was screened as a differentially expressed gene in The Cancer Genome Atlas (TGCA) database, the correlations of its expression level with the clinical parameters and prognosis of patients with OSCC were analyzed. The outcomes of the multivariate analysis were used to construct a nomogram, and the accuracy of the model was evaluated with the calibration curve. The GeneMANIA and STRING databases were used to generate network diagrams depicting interactions of genes with CHD4, and heat maps of genes co-expressed with CHD4 were generated using the TCGA database. TargetScan was then used to look into the miRNAs that interact with the 3' untranslated region of CHD4 mRNA. Finally, GSEA enrichment analysis was used to explore the possible mechanism. Results The differentially expressed molecule CHD4 was screened by TCGA database for OSCC. CHD4 was overexpressed in OSCC tumor tissues, and OSCC patients with low expression of CHD4 have better OS and DSS. The nomogram had a C-index of 0.575 (0.548–0.602), which indicated some degree of predictive reliability. CHD4 has certain correlation with exons of OSCC related genes, including TP53 , NOTCH1 , CASP8 , PTEN , TP63 , ANXA1 , CDH1 , CTNNB1 , GDF15 and EGFR . According to the TargetScan database, hsa-miR-194-5p is the miRNA that regulates CHD4 upstream the most. GSEA analysis showed that CHD4 may participate in the poor prognosis of OSCC by participating in PI3K/AKT pathway, protein adhesion regulation, MAPK pathway, cytokine and inflammatory response regulation, angiogenesis and platelet regulation. Conclusions The decreased expression of CHD4 may indicate a better prognosis in OSCC patients and could serve as a novel predictive biomarker for OSCC. Also, hsa-miR-194-5p was found to contribute to the poor prognosis of OSCC by regulating CHD4 and enhancing tumor anoikis resistance via the PI3K/AKT signaling pathway. These findings suggest that CHD4 might be a therapeutic target for the effective treatment of OSCC.

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Section: Discussionmentioning

confidence: 99%

“…The expression of CHD4 24). However, a common feature of tumor development and growth is the viability of transformed cells under "independent" growth conditions.…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics based exploration of hsa-miR-194-5p regulation of CHD4 through PI3K/AKT signal pathway to enhance tumor resistance to apoptosis due to loss of nests and participate in poor prognosis of oral squamous cell carcinoma

Li¹,

Wang²,

Shen³

et al. 2023

Ann Transl Med

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“…Meanwhile, the frequent overexpression and/or hyperactivation of Rac1 happens in chemo-resistant tumors [20]. XRCC5 (X-Ray Repair Cross Complementing 5) plays the relative role of DNA repair as a biomarker for the prognosis of multiple cancers, and potential therapy application to anticancer drug discovery [21,22].…”

Section: Discussionmentioning

confidence: 99%

A Novel Anoikis-revelant Gene Signature for Prognosis Prediction and Tumor Immune Microenvironment in Lung Adenocarncinoma

Ma¹,

Li²,

Xue³

et al. 2022

Preprint

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Background: Anoikis is an apoptotic cell death, which is resulting from the loss of interaction between cells and the extracellular matrix, and has served a prominent role in metastasis. The aim of the present study was to identify an anoikis-revelant genes (ARGs) signature for Lung Adenocarncinoma (LUAD) patients’ prognosis and explore the underlying molecular mechanisms. Methods: In the training cohort, LUAD patients from The Cancer Genome Atlas (TCGA) were used, and Gene Expression Omnibus (GEO) cohort GSE72094 was used for validation. A total of 508 anoikis-revelant genes downloaded from the GeneCards. Univariate Cox analysis was applied for preliminary screening of anoikis-revelant genes with potential prognostic capacity in the training cohort. These genes were then applied into an overall survival-based LASSO regression model, building a gene signature. The discovered gene signature was then evaluated via Kaplan–Meier (KM), Cox, and ROC analyses in both cohorts. To better explore the functional annotation of the gene signature and the character of tumor microenvironment, the GSEA enrichment and CIBERSORT algorithm were performed. Results: A thirteen-gene signature was built in the TCGA-LUAD cohort and further validated in GSE72094 cohort, revealing its independent prognosis value in LUAD. Next, the signature's predictive ability for LUAD prognosis was confirmed through ROC analysis. Moreover, analyses of gene enrichment and immune infiltrating detailed exhibited cell adhesion and VEGF pathways related with the thirteen-gene signature, also showing that M0 macrophages, mast cells, dendritic cells and CD4+ memory T cells involved in the prognosis of the thirteen-gene signature. Conclusions: An inventive anoikis-revelant thirteen-gene signature (ABHD4, CDCP1, CDK1, CENPF, EIF2AK3, FADD, FYN, HGF, OGT, PIK3CG, PPP2CA, RAC1, and XRCC5) was generated through this study. It could accurately predict LUAD prognosis and was related to M0 macrophages, mast cells, dendritic cells, and CD4+ memory T cells.

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“…It prevents dysplastic cells, pre-cancerous epithelial cells, from departing from their primary location and spreading elsewhere, avoiding the aggressive behavior of the detached tumor cells ( Taddei et al, 2012 ). Anoikis resistance, which is the breakdown or avoidance of anoikis, is expected to confer selective superiority upon the detached cancer cells, affording them an increased anchorage-independent survival time, thereby facilitating eventual reattachment and uncontrolled growth of other sites ( Frisch and Screaton, 2001 ; Guadamillas et al, 2011 ; Khan et al, 2022 ). Anoikis is envisioned as a pivotal defense in combating tumor metastasis and maintaining normal tissue homeostasis ( Kim et al, 2012 ; Paoli et al, 2013 ).…”

Section: Introductionmentioning

confidence: 99%

Construction of an original anoikis-related prognostic model closely related to immune infiltration in gastric cancer

Zhao

et al. 2023

Front. Genet.

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Background: Anoikis is considered as a particular type of programmed cell death, the weakness or resistance of which contributes greatly to the development and progression of most malignant solid tumors. However, the latent impact of anoikis-related genes (ARGs) on gastric cancer (GC) is still ambiguous. Based on these, this study established an anoikis-related prognostic model of GC to identify the prognosis of patients and provide more effective treatment in clinical practice.Methods: First, we extracted four public datasets containing the gene expression and clinicopathological information of GC, which were worked as the training and validating sets, separately. Then, an anoikis-related survival-predicted model of GC was developed via Lasso and COX regression analyses and verified by using the Kaplan-Meier (KM) curve and receiver operating characteristic (ROC) curve analyses. Next, we assigned GC patients to two groups characterized by the risk score calculated and analyzed somatic mutation, functional pathways, and immune infiltration between the different two groups. Finally, a unique nomogram was offered to clinicians to forecast the personal survival probability of GC patients.Results: Based on seven anoikis-related markers screened and identified, a carcinogenic model of risk score was produced. Patients placed in the high-score group suffered significantly worse overall survival (OS) in four cohorts. Additionally, the model revealed a high sensitivity and specificity to prognosticate the prognoses of GC patients [area under the ROC curve (AUC) at 5-year = 0.713; GSE84437, AUC at 5-year = 0.639; GSE15459, AUC at 5-year = 0.672; GSE62254, AUC at 5-year = 0.616]. Apart from the excellent predictive performance, the model was also identified as an independent prediction factor from other clinicopathological characteristics. Combining anoikis-related prognostic model with GC clinical features, we built a more comprehensive nomogram to foresee the likelihood of survival of GC patients in a given year, showing a well-accurate prediction performance.Conclusion: In summary, this study created a new anoikis-related signature for GC, which has potentially provided new critical insights into survival prediction and individualized therapy development.

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Understanding the cell survival mechanism of anoikis-resistant cancer cells during different steps of metastasis

Cited by 78 publications

References 109 publications

Bioinformatics based exploration of hsa-miR-194-5p regulation of CHD4 through PI3K/AKT signal pathway to enhance tumor resistance to apoptosis due to loss of nests and participate in poor prognosis of oral squamous cell carcinoma

Bioinformatics based exploration of hsa-miR-194-5p regulation of CHD4 through PI3K/AKT signal pathway to enhance tumor resistance to apoptosis due to loss of nests and participate in poor prognosis of oral squamous cell carcinoma

A Novel Anoikis-revelant Gene Signature for Prognosis Prediction and Tumor Immune Microenvironment in Lung Adenocarncinoma

Construction of an original anoikis-related prognostic model closely related to immune infiltration in gastric cancer

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