Inhibin β-A (INHBA) induces epithelial–mesenchymal transition and accelerates the motility of breast cancer cells by activating the TGF-β signaling pathway

Yu, Yingying; Wang, Weiwei; Lu, Wenying; Chen, Wei; Shang, Anquan

doi:10.1080/21655979.2021.1957754

Cited by 35 publications

(38 citation statements)

References 42 publications

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“…Among the first ten top-ranked primary INHBA interactors in the STRING protein-protein interaction (PPI) network, most genes were involved in the TGF- β signaling pathway. Previous studies have also demonstrated that INHBA plays a role in the regulation of cancer cell growth, proliferation, and survival via the TGF- β signaling pathway Chen et al (2019) ; Yu et al (2021) ; Basu et al (2015) . GO and GSEA analysis revealed that INHBA -related genes were associated with extracellular matrix, collagen formation and degradation, the misregulation of which is a key factor in epithelial to mesenchymal transition (EMT) Burke et al (2015) .…”

Section: Disscusionmentioning

confidence: 97%

mentioning

confidence: 99%

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INHBA is a Prognostic Biomarker and Correlated With Immune Cell Infiltration in Cervical Cancer

Zhao

et al. 2022

Front. Genet.

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Background: Inhibin A (INHBA), a member of the TGF-β superfamily, has been shown to be differentially expressed in various cancer types and is associated with prognosis. However, its role in cervical cancer remains unclear.Methods: We aimed to demonstrate the relationship between INHBA expression and pan-cancer using The Cancer Genome Atlas (TCGA) database. Next, we validated INHBA expression in cervical cancer using the Gene Expression Omnibus (GEO) database, including GSE7803, GSE63514, and GSE9750 datasets. Enrichment analysis of INHBA was performed using the R package “clusterProfiler.” We analyzed the association between immune infiltration level and INHBA expression in cervical cancer using the single-sample gene set enrichment analysis (ssGSEA) method by the R package GSVA. We explored the association between INHBA expression and prognosis using the R package “survival”.Results: Pan-cancer data analysis showed that INHBA expression was elevated in 19 tumor types, including cervical cancer. We further confirmed that INHBA expression was higher in cervical cancer samples from GEO database and cervical cancer cell lines than in normal cervical cells. Survival prognosis analysis indicated that higher INHBA expression was significantly associated with reduced Overall Survival (p = 0.001), disease Specific Survival (p = 0.006), and Progression Free Interval (p = 0.001) in cervical cancer and poorer prognosis in other tumors. GSEA and infiltration analysis showed that INHBA expression was significantly associated with tumor progression and some types of immune infiltrating cells.Conclusion:INHBA was highly expressed in cervical cancer and was significantly associated with poor prognosis. Meanwhile, it was correlated with immune cell infiltration and could be used as a promising prognostic target for cervical cancer.

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Section: Disscusionmentioning

confidence: 97%

mentioning

confidence: 99%

INHBA is a Prognostic Biomarker and Correlated With Immune Cell Infiltration in Cervical Cancer

Zhao

et al. 2022

Front. Genet.

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“…INHBA is reported to be involved in cell growth, proliferation, apoptosis, metastasis, and carcinogenesis [29][30][31][32]39]. INHBA is involved in various physiological processes through autocrine and paracrine functions [40,41].…”

Section: Discussionmentioning

confidence: 99%

“…According to several studies, the overexpression of INHBA is associated with lung, esophageal, colon, gastric, prostate, and urothelial carcinoma [23][24][25][26][27][28]. INHBA has been identified to have a crucial role in malignant biological behavior, including proliferation, migration, invasion, and metastasis [29][30][31][32]. Previous studies revealed that the overexpression of INHBA may be affected by promoter methylation in cancer [23,24,26].…”

Section: Introductionmentioning

confidence: 99%

DNA Hypomethylation Is Associated with the Overexpression of INHBA in Upper Tract Urothelial Carcinoma

Kao

Chang

Liu

et al. 2022

IJMS

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Urothelial carcinoma includes upper urinary tract cancer (UTUC) and bladder cancer. Although nephroureterectomy is the standard treatment for UTUC, the recurrence rate is approximately half and the tumor is associated with poor prognoses. Metastases are the most devastating and lethal clinical situation in urothelial carcinoma. Despite its clinical importance, few potential diagnostic biomarkers are suitable for early UC detection. We compared high-stage/high-grade urothelial carcinoma tissues to adjacent normal urothelial tissues using methyl-CpG binding domain protein capture for genome-wide DNA methylation analysis. Based on our findings, inhibin βA (INHBA) might be associated with carcinogenesis and metastasis. Further, clinical UC specimens had significant INHBA hypomethylation based on pyrosequencing. INHBA was detected by real-time PCR and immunohistochemistry staining, and was found to be highly expressed in clinical tissues and cell lines of urothelial carcinoma. Further, INHBA depletion was found to significantly reduce BFTC-909 cell growth and migration by INHBA-specific small interfering RNA. Interestingly, a positive correlation was found between SMAD binding and extracellular structure organization with INHBA using gene set enrichment analysis and gene ontology analysis. Together, these results are the first evidence of INHBA promoter hypomethylation and INHBA overexpression in UTUC. INHBA may affect urothelial carcinoma migration by reorganizing the extracellular matrix through the SMAD pathway.

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“…Significantly, the induction of EMT is associated with tumor aggressiveness and poor prognostic outcomes in breast cancer patients [ 65 , 66 ]. The role of chemokines in EMT induction in epithelial tumor cells has been investigated [ 67 , 68 ], and the evidence has implicated CCL20 in such processes [ 69 ]. In vitro study has demonstrated that direct coculture between healthy breast cells and recombinant human CCL20 upregulates vimentin and N-cadherin, which are characteristics of EMT.…”

Section: Role Of Ccl20 In Breast Cancer Progressionmentioning

confidence: 99%

Multifaceted roles of CCL20 (C-C motif chemokine ligand 20): mechanisms and communication networks in breast cancer progression

et al. 2021

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Emerging studies have demonstrated notable roles of CCL20 in breast cancer progression. Based on these findings, CCL20 has become a potential therapeutic target for cancer immunotherapy. Accordingly, studies utilizing monoclonal antibodies to target CCL20 are currently being experimented. However, the existence of cytokine network in the tumor microenvironment collectively regulates tumor progression. Hence, a deeper understanding of the role of CCL20 and the underlying signaling pathways regulating the functions of CCL20 may provide a novel strategy for therapeutic interventions. This review provides the current knowledge on how CCL20 interacts with breast cancer cells to influence tumor progression via immunosuppression, angiogenesis, epithelial to mesenchymal transition, migration/invasion and chemoresistance. As a possible candidate biomarker, we also reviewed signal pathways and other factors in the tumor microenvironment regulating the tumor-promoting functions of CCL20.These new insights may be useful to design new potent and selective CCL20 inhibitors against breast cancer in the future.

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Inhibin β-A (INHBA) induces epithelial–mesenchymal transition and accelerates the motility of breast cancer cells by activating the TGF-β signaling pathway

Abstract: Inhibin β-A (INHBA) induces epithelial-mesenchymal transition and accelerates the motility of breast cancer cells by activating the TGF-β signaling pathway,

Cited by 35 publications

References 42 publications

INHBA is a Prognostic Biomarker and Correlated With Immune Cell Infiltration in Cervical Cancer

INHBA is a Prognostic Biomarker and Correlated With Immune Cell Infiltration in Cervical Cancer

DNA Hypomethylation Is Associated with the Overexpression of INHBA in Upper Tract Urothelial Carcinoma

Multifaceted roles of CCL20 (C-C motif chemokine ligand 20): mechanisms and communication networks in breast cancer progression

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