Dataset Information

FZD6 Promotes Melanoma Cell Invasion but Not Proliferation by Regulating Canonical Wnt Signaling and Epithelial‒Mesenchymal Transition.

ABSTRACT: FZD6 is a key gene that controls tissue polarity during development. Increasing evidence suggests that it also plays active roles in various cancers. In this study, we show that FZD6 is overexpressed in multiple melanoma cell lines and human samples. Knockdown or knockout of FZD6 does not affect cell proliferation but significantly reduces the invasive ability of melanoma cells. In addition, we have found that knockout of Fzd6 dramatically reduces lung metastasis in the Pten/BRaf mouse model of melanoma. Mechanistic studies in vitro and in vivo reveal a surprising involvement of canonical Wnt signaling and epithelial‒mesenchymal pathway in the FZD6-mediated invasive phenotype. Together, our study supports a promoter role of FZD6 in melanoma progression.

SUBMITTER: Dong B

PROVIDER: S-EPMC10292634 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature

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FZD6 Promotes Melanoma Cell Invasion but Not Proliferation by Regulating Canonical Wnt Signaling and Epithelial‒Mesenchymal Transition.

Dong Bo B Simonson Laura L Vold Samantha S Oldham Ethan E Barten Lillian L Ahmad Nihal N Chang Hao H

The Journal of investigative dermatology 20221109 4

FZD6 is a key gene that controls tissue polarity during development. Increasing evidence suggests that it also plays active roles in various cancers. In this study, we show that FZD6 is overexpressed in multiple melanoma cell lines and human samples. Knockdown or knockout of FZD6 does not affect cell proliferation but significantly reduces the invasive ability of melanoma cells. In addition, we have found that knockout of Fzd6 dramatically reduces lung metastasis in the Pten/BRaf mouse model of ...[more]

PMID: 36368445

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Project description:Osteosarcoma (OS) is a rare type of tumor and mostly occurs in children and adolescents. Approximately 10‑25% of patients with OS have lung metastases, and lung damage caused by lung metastasis is the main cause of mortality. Therefore, studying the growth and metastasis of OS is key in reducing OS mortality and improving prognosis. The expression of long non‑coding RNA (lncRNA) cancer susceptibility 15 (CASC15) in OS patients or OS cell lines were quantified by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). The expression of vimentin, E‑cadherin, N‑cadherin, and cyclin D were detected by RT‑qPCR and western blotting. Mice were injected with OS cell lines via the tail vein to observe tumor formation in the lung. CCK‑8 and EdU assays were utilized to evaluate cell proliferation. Both Ttranswell assay and cell scratch test detected cell migration. The results revealed that lncRNA‑CASC15 was highly expressed in clinical samples and OS cells. In vitro verification experiments revealed that CASC15 promoted the growth of OS cells. Rescue experiments demonstrated that CASC15 affected the cell cycle by activating the Wnt/β‑catenin pathway, thereby promoting cell proliferation. Furthermore, the transfection dose test indicated that lentiviruses expressing various doses of CASC15‑overexpression (oe‑CASC15) altered the proliferation and migration status of OS cells. CASC15 promoted OS cell metastasis both in vivo and in vitro. The overexpression of CASC15 revealed that the occurrence of metastasis was also related to the Wnt/β‑catenin pathway. The western blotting results revealed that CASC15 could lead to β‑catenin entering the nucleus via the Wnt pathway to promote the epithelial‑mesenchymal transition (EMT) of OS cells. To sum up, CASC15 promoted the proliferation of OS cells in vitro and the growth of OS xenograft tumors in vivo. Moreover, CASC15 promoted the entry of β‑catenin into the nucleus, thus activating the Wnt pathway and subsequently promoting the EMT of OS cells.

Dataset Information

FZD6 Promotes Melanoma Cell Invasion but Not Proliferation by Regulating Canonical Wnt Signaling and Epithelial‒Mesenchymal Transition.

Publications

FZD6 Promotes Melanoma Cell Invasion but Not Proliferation by Regulating Canonical Wnt Signaling and Epithelial‒Mesenchymal Transition.

Similar Datasets

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