Paradoxical roles of TGF-&amp;beta; signaling in suppressing and promoting squamous cell carcinoma

Wu, Fanglong; Weigel, Kelsey; Zhou, Hongmei; Wang, Xiaojing

doi:10.1093/abbs/gmx127

Cited by 54 publications

(44 citation statements)

References 72 publications

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“…The activated TGF‐β binds to TGF‐β type II receptor (TGF‐βRII) and further phosphorylates TGF‐β type I receptor (TGF‐βRI). The binding of TGF‐βRII and TGF‐βRI promotes the downstream signalling by phosphorylating cytoplasm mediators, SMAD2 and SMAD3, which complex with SMAD4 and translocate into the nucleus and regulate the transcriptions of target genes . Our data here have proposed the evidences that MMP‐9 in the breast cell lines regulates the phosphorylation of SMAD2/3 and increases the cellular levels of SMADs.…”

Section: Discussionmentioning

confidence: 54%

Overexpression of matrix metalloproteinase‐9 in breast cancer cell lines remarkably increases the cell malignancy largely via activation of transforming growth factor beta/SMAD signalling

et al. 2019

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Objectives: Matrix metalloproteinase 9 (MMP-9) has been frequently noticed in the breast cancers. In this study, we aim to investigate the associations of MMP-9 with the activation of transforming growth factor beta (TGF-β)/SMAD signalling and the malignancy of breast malignant tumour cells. Materials and methods:The distributions of MMP-9 and TGF-β in the tissues of canine breast cancers were screened by immunohistochemical assays. A recombinant plasmid expressing mouse MMP-9 was generated and transiently transfected into three different breast cancer cell lines. Cell Counting Kit-8 and colony formation assay were used to study cell viability. Migration and invasion ability were analysed by wound assay and transwell filters. Western blot and quantitative real-time PCR were used to determine the protein and mRNA expression.Result: Remarkable strong MMP-9 and TGF-β signals were observed in the malignant tissues of canine breast cancers. In the cultured three cell lines receiving recombinant plasmid expressing mouse MMP-9, the cell malignancy was markedly increased, including the cell colony formation, migration and epithelial-mesenchymal transition.The levels of activated TGF-β, as well as SMAD4, SMAD2/3 and phosphorylation of SMAD2, were increased, reflecting an activation of TGF-β/SMAD signalling. We also demonstrated that the inhibitors specific for MMP-9 and TGF-β sufficiently blocked the overexpressing MMP-9 induced the activation of SMAD signalling and enhancement on invasion in the tested breast cancer cell lines. Conclusion:Overexpression of MMP-9 increases the malignancy of breast cancer cell lines, largely via activation of the TGF-β/SMAD signalling.

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Section: Discussionmentioning

confidence: 54%

Overexpression of matrix metalloproteinase‐9 in breast cancer cell lines remarkably increases the cell malignancy largely via activation of transforming growth factor beta/SMAD signalling

et al. 2019

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“…This result further suggested that HOXC6 was likely to promote OSCC development. Previous studies of OSCC-related signaling pathways revealed that the TGF-β signaling pathway was closely related to OSCC development [18,19]. However, little is known about whether HOXC6 regulates the TGF-β signaling pathway in OSCC.…”

Section: Resultsmentioning

confidence: 99%

MicroRNA-495 confers inhibitory effects on cancer stem cells in oral squamous cell carcinoma through the HOXC6-mediated TGF-β signaling pathway

et al. 2020

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Background: Oral squamous cell carcinoma (OSCC) is associated with high morbidity and ranks sixth among malignancies worldwide. Increasing evidence suggests that microRNAs (miRNAs or miRs) play a critical role in regulating cancer stem cells (CSCs), which drive the proliferation and spread of OSCC. Therefore, based on the alteration of aberrantly expressed miR-495 and homeobox C6 (HOXC6) by Gene Expression Omnibus (GEO) analysis, we subsequently explore the potential effect of miR-495 on the progression of CSCs in OSCC. Methods: After the isolation of CSCs from the clinical tissue samples of OSCC patients, the expression of miR-495 and HOXC6 was determined, followed by the validation of the relationship between miR-495 and HOXC6. Subsequently, gain-and loss-function approach was performed to detect the role of miR-495 and HOXC6 in cell proliferation, migration, invasion, cell cycle entry, apoptosis, and epithelial-mesenchymal transition (EMT) of CSCs in OSCC, as well as the tumor growth in vivo. Results: HOXC6 was highly expressed while miR-495 was poorly expressed in OSCC. HOXC6 was verified to be a target gene of miR-495, and miR-495 could inhibit the activation of the TGF-β signaling pathway. CSCs with miR-495 overexpression or HOXC6 silencing exhibited reversed EMT process; reduced abilities of proliferation, migration, and invasion; and promoted cell apoptosis in vitro. Moreover, inhibited tumor growth was observed in vivo after injection with miR-495 agomir or sh-HOXC6. In contrast, the downregulation of miR-495 showed an induced role in the progression of OSCC. Conclusion: These findings suggest that miR-495 may suppress HOXC6 to inhibit EMT, proliferation, migration, and invasion while promoting apoptosis of CSCs in OSCC by inhibiting the TGF-β signaling pathway.

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“…The expression changes of miR-125b altered the abundance of its target BAK1 which may control the apoptotic pathway in oral cancer (45). (37) and PI3K-Akt signaling pathway was also considered important to the development of OSCC (35). In summary, HCP5 may have the potential to become a novel biomarker for detection and diagnosis of oral cancer.…”

Section: Discussionmentioning

confidence: 99%

Construction and analysis of the lncRNA-miRNA-mRNA network based on competitive endogenous RNA reveal functional lncRNAs in oral cancer

Yin

Zeng

et al. 2020

Preprint

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Background There is a growing body of evidence suggesting that long non-coding RNAs(lncRNAs) can function as a microRNA(miRNA) sponge in various diseases including oral cancer. However, we are still not very clear about the pathophysiological function of lncRNAs. Methods We constructed a lncRNA-miRNA-mRNA network in oral cancer based on the competitive endogenous RNA(ceRNA) theory with the human expression profiles GSE74530 from the Gene Expression Omnibus (GEO) database and used topological analysis to determine the hub lncRNAs in the regulatory ceRNA network. Then, function enrichment analysis was performed by R package Cluster Profiler. Results A total of 238 potential co-dysregulated competing triples were obtained in the lncRNA-assoicated ceRNA network of oral cancer, which consisted of 10 lncRNA nodes, 41 miRNA nodes, and 122 mRNA nodes. Additionally, we found three lncRNAs( HCP5 , AGAP11 , HCG22 ) exhibiting superior potential as diagnostic and prognostic markers of oral cancer. Conclusions Our findings will provide novel insights for understanding the ceRNA regulation in oral cancer and identify three novel lncRNAs as potential molecular biomarkers.

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Paradoxical roles of TGF-β signaling in suppressing and promoting squamous cell carcinoma

Cited by 54 publications

References 72 publications

Overexpression of matrix metalloproteinase‐9 in breast cancer cell lines remarkably increases the cell malignancy largely via activation of transforming growth factor beta/SMAD signalling

Overexpression of matrix metalloproteinase‐9 in breast cancer cell lines remarkably increases the cell malignancy largely via activation of transforming growth factor beta/SMAD signalling

MicroRNA-495 confers inhibitory effects on cancer stem cells in oral squamous cell carcinoma through the HOXC6-mediated TGF-β signaling pathway

Construction and analysis of the lncRNA-miRNA-mRNA network based on competitive endogenous RNA reveal functional lncRNAs in oral cancer

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