Nodal regulates bladder cancer cell migration and invasion via the ALK/Smad signaling pathway

Li, Youkong; Zhong, Wen; Zhu, Min; Hu, Shengguo; Su, Xiaokang

doi:10.2147/ott.s177514

Cited by 11 publications

(7 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…39 Conversely, ALK7 exerts tumor-promoting effects in bladder cancer and retinoblastoma. 40,41 However, little is documented concerning the role of ALK7 in NPC. Our results suggested that ALK7 may serve as a tumor suppressor in NPC, given that it was identified as a direct target of the tumor-promoting gene BART10-3p both in vitro and in vivo and that ectopic expression of ALK7 could reverse the oncogenic effects of BART10-3p.…”

Section: Discussionmentioning

confidence: 99%

“…[32][33][34] Prior studies have implicated ALK7 in human tissue morphogenesis, metabolic disorders, and tumorigenesis. [35][36][37][38][39][40][41] Similar to the bidirectional functions of ALK7 in stem cell differentiation under different conditions, ALK7 has contrasting roles in different tumors. The ALK7 signaling is found to impair metastasis in breast and pancreatic neuroendocrine tumors, 37 suppress proliferation and chemoresistance in ovarian cancer, 38 and induce apoptosis in hepatoma.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Epstein-Barr virus microRNA BART10-3p promotes dedifferentiation and proliferation of nasopharyngeal carcinoma by targeting ALK7

Luo

Zou

et al. 2021

Exp Biol Med (Maywood)

View full text Add to dashboard Cite

Non-keratinizing nasopharyngeal carcinoma, the major subtype of nasopharyngeal carcinoma, is characterized by low differentiation and a close relation to Epstein-Barr virus infection, which indicates a link between Epstein-Barr virus oncogenesis and loss of differentiation, and raises our interest in investigating the involvement of Epstein-Barr virus in nasopharyngeal carcinoma dedifferentiation. Our previous study showed abundant expression of an Epstein-Barr virus-encoded microRNA, BART10-3p, in nasopharyngeal carcinoma tissues, but the association between BART10-3p and nasopharyngeal carcinoma differentiation remains unknown. Here, we examined the expression and prognostic value of BART10-3p, and undertook bioinformatics analysis and functional assays to investigate the influence of BART10-3p on nasopharyngeal carcinoma differentiation and proliferation and the underpinning mechanism. Microarray analysis identified BART10-3p as the most significantly upregulated Epstein-Barr virus-encoded microRNA in nasopharyngeal carcinoma tissues and the upregulation was confirmed in two public datasets. The expression of BART10-3p was an independent unfavorable prognosticator in nasopharyngeal carcinoma and its integration with the clinical stage showed improved prognosis predictive performance. Bioinformatics analysis suggested a potential role of BART10-3p in tumor differentiation and progression. Functional assays demonstrated that BART10-3p could promote nasopharyngeal carcinoma cell dedifferentiation, epithelial-mesenchymal transition, and proliferation in vitro, and tumorigenicity in vivo. Mechanistically, BART10-3p directly targeted the 3′UTR of ALK7 and suppressed its expression. Reconstitution of ALK7 rescued BART10-3p-induced malignant phenotypes. Overall, our study demonstrates that BART10-3p promotes dedifferentiation and proliferation of nasopharyngeal carcinoma by targeting ALK7, suggesting a promising therapeutic opportunity to reverse the malignant phenotypes of nasopharyngeal carcinoma.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Epstein-Barr virus microRNA BART10-3p promotes dedifferentiation and proliferation of nasopharyngeal carcinoma by targeting ALK7

Luo

Zou

et al. 2021

Exp Biol Med (Maywood)

View full text Add to dashboard Cite

show abstract

“…In other words, NODAL inhibits cell proliferation and induces apoptosis by activating ALK7( 27 ). Li et al ( 28 ) reported that in bladder cancer tissues and cell lines, NODAL knockdown blocked the expression of ALK7. Additionally, an ALK7 inhibitor reversed the effect of NODAL overexpression on bladder cancer cell proliferation, invasion and migration.…”

Section: Discussionmentioning

confidence: 99%

Biological effects of NODAL on endometrial cancer cells and its underlying mechanisms

et al. 2021

View full text Add to dashboard Cite

Activin A receptor type 1C (ALK7) and its ligand nodal growth differentiation factor (NODAL) serve numerous roles in cancer cells, including regulating cancer invasion, migration and apoptosis. NODAL promotes breast cancer cell apoptosis by activating ALK7; however, ALK7 and NODAL expression in endometrial cancer (EC), as well as their effects and underlying mechanisms in EC cells, are not completely understood. The present study aimed to characterize the expression of NODAL and ALK7 in EC, as well as the underlying mechanisms. The expression levels of ALK7 and NODAL were detected via reverse transcription-quantitative PCR and western blotting. Cell transfection was performed to overexpress NODAL or interfere ALK7. Cell proliferation, invasion and migration were detected via Cell Counting Kit-8, Transwell and wound healing assays, respectively. Flow cytometry was performed to detect cell apoptosis and western blotting was conducted to detect the expression levels of apoptosis-related proteins. NODAL and ALK7 expression levels were significantly decreased in EC cell lines compared with normal endometrial cells. NODAL overexpression inhibited EC cell proliferation, invasion and migration, and promoted EC cell apoptosis compared with the overexpression-negative control (Ov-NC) group. Moreover, NODAL overexpression significantly increased ALK7 expression levels in EC cells compared with the Ov-NC group. ALK7 reversed NODAL overexpression-mediated inhibition of EC cell proliferation, invasion and migration, and promotion of EC cell apoptosis. The present study indicated that NODAL inhibited EC cell proliferation, invasion and migration, and promoted EC cell apoptosis by activating ALK7.

show abstract

“…However, aberrant re-expression of Nodal has a prominent role in tumorigenesis and metastasis in melanoma, glioma, breast, prostate, and pancreatic cancers, with expression levels being directly proportional to tumor grade [16, 18, 19, 32]. Interestingly, a recent report shows that suppression of Nodal significantly reduced growth, clonogenicity, migration and invasion in bladder cancer cells [20]. Surprisingly, when we stimulated WERI Rb1 and Y79 cells with exogenous Nodal at 100, 300, 500 ng/mL, we did not observe any further increase in SMAD2 phosphorylation [3].…”

Section: Discussionmentioning

confidence: 99%

Downregulation of Nodal inhibits metastatic progression in retinoblastoma

Asnaghi

White

Yoon

et al. 2019

acta neuropathol commun

View full text Add to dashboard Cite

Retinoblastoma is the most common intraocular malignancy in children. We previously found that the ACVR1C/SMAD2 pathway is significantly upregulated in invasive retinoblastoma samples from patients. Here we studied the role of an ACVR1C ligand, Nodal, in regulating growth and metastatic dissemination in retinoblastoma. Inhibition of Nodal using multiple short hairpin (shRNAs) in WERI Rb1 and Y79 retinoblastoma cell cultures reduced growth by more than 90%, as determined by CCK-8 growth assay. Proliferation was also significantly inhibited, as found by Ki67 assay. These effects were paralleled by inhibition in the phosphorylation of the downstream effector SMAD2, as well as induction of apoptosis, as we observed more than three-fold increase in the percentage of cells positive for cleaved-caspase-3 or expressing cleaved-PARP1. Importantly, we found that downregulation of Nodal potently suppressed invasion in vitro, by 50 to 80%, as determined by transwell invasion assay ( p = 0.02). Using an orthotopic model of retinoblastoma in zebrafish, we found 34% reduction in the ability of the cells to disseminate outside the eye, when Nodal was knocked down by shRNA ( p = 0.0003). These data suggest that Nodal plays an important role in promoting growth, proliferation and invasion in retinoblastoma, and can be considered a new therapeutic target for both primary tumor growth and metastatic progression.

show abstract

Nodal regulates bladder cancer cell migration and invasion via the ALK/Smad signaling pathway

Cited by 11 publications

References 28 publications

Epstein-Barr virus microRNA BART10-3p promotes dedifferentiation and proliferation of nasopharyngeal carcinoma by targeting ALK7

Epstein-Barr virus microRNA BART10-3p promotes dedifferentiation and proliferation of nasopharyngeal carcinoma by targeting ALK7

Biological effects of NODAL on endometrial cancer cells and its underlying mechanisms

Downregulation of Nodal inhibits metastatic progression in retinoblastoma

Contact Info

Product

Resources

About