Cargando…

Downregulation of KCTD12 contributes to melanoma stemness by modulating CD271

OBJECTIVE: Cancer metastasis remains the primary cause of cancer-related death worldwide. In a previous study, we found that levels of BTB/POZ domain-containing protein KCTD12 are lower in metastatic melanoma cells than in parental melanoma cells. The purpose of this study was to identify the roles...

Descripción completa

Detalles Bibliográficos
Autores principales: Shen, Weiyu, Li, Yumei, Li, Bifei, Zheng, Liping, Xie, Xiaodong, Le, Jingqing, Lu, Yusheng, Li, Tao, Chen, Fan, Jia, Lee
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Chinese Anti-Cancer Association 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6743620/
https://www.ncbi.nlm.nih.gov/pubmed/31565480
http://dx.doi.org/10.20892/j.issn.2095-3941.2019.0073
_version_ 1783451300636131328
author Shen, Weiyu
Li, Yumei
Li, Bifei
Zheng, Liping
Xie, Xiaodong
Le, Jingqing
Lu, Yusheng
Li, Tao
Chen, Fan
Jia, Lee
author_facet Shen, Weiyu
Li, Yumei
Li, Bifei
Zheng, Liping
Xie, Xiaodong
Le, Jingqing
Lu, Yusheng
Li, Tao
Chen, Fan
Jia, Lee
author_sort Shen, Weiyu
collection PubMed
description OBJECTIVE: Cancer metastasis remains the primary cause of cancer-related death worldwide. In a previous study, we found that levels of BTB/POZ domain-containing protein KCTD12 are lower in metastatic melanoma cells than in parental melanoma cells. The purpose of this study was to identify the roles of KCTD12 in cancer metastasis. METHODS: The Cancer Genome Atlas (TCGA) datasets were used to evaluate the relationship between KCTD12 and skin cutaneous melanoma (SKCM) prognosis. The effects of endogenous KCTD12 on biological behaviors were examined using the MTT assay. The impacts of KCTD12 on melanoma stemness were explored using spheroid formation assay. KCTD12 knockout A375 cells were generated to confirm the inhibitory effect of KCTD12 on CD271, and a mouse metastatic model was used to determine the impact of KCTD12 on melanoma metastasis in vivo. RESULTS: KCTD12 levels were lower in lung metastatic cells than in paired parental melanoma cells, and low KCTD12 expression indicated a poor prognosis in SKCM. Cancer metastasis-related capacities were higher in lung metastatic cells than in parental melanoma cells. Moreover, KCTD12 knockdown enhanced tumor growth and metastasis both in vitro and in vivo. Mechanistically, the interaction between KCTD12 and CD271 might be responsible for the stemness transformation after KCTD12 knockdown. CONCLUSIONS: This study identifies for the first time the role of the interaction between KCTD12 and CD271 in inducing melanoma cell stemness transformation. Moreover, KCTD12 repression enhances melanoma cell growth, adhesion, migration and invasion.
format Online
Article
Text
id pubmed-6743620
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher Chinese Anti-Cancer Association
record_format MEDLINE/PubMed
spelling pubmed-67436202019-09-27 Downregulation of KCTD12 contributes to melanoma stemness by modulating CD271 Shen, Weiyu Li, Yumei Li, Bifei Zheng, Liping Xie, Xiaodong Le, Jingqing Lu, Yusheng Li, Tao Chen, Fan Jia, Lee Cancer Biol Med Original Article OBJECTIVE: Cancer metastasis remains the primary cause of cancer-related death worldwide. In a previous study, we found that levels of BTB/POZ domain-containing protein KCTD12 are lower in metastatic melanoma cells than in parental melanoma cells. The purpose of this study was to identify the roles of KCTD12 in cancer metastasis. METHODS: The Cancer Genome Atlas (TCGA) datasets were used to evaluate the relationship between KCTD12 and skin cutaneous melanoma (SKCM) prognosis. The effects of endogenous KCTD12 on biological behaviors were examined using the MTT assay. The impacts of KCTD12 on melanoma stemness were explored using spheroid formation assay. KCTD12 knockout A375 cells were generated to confirm the inhibitory effect of KCTD12 on CD271, and a mouse metastatic model was used to determine the impact of KCTD12 on melanoma metastasis in vivo. RESULTS: KCTD12 levels were lower in lung metastatic cells than in paired parental melanoma cells, and low KCTD12 expression indicated a poor prognosis in SKCM. Cancer metastasis-related capacities were higher in lung metastatic cells than in parental melanoma cells. Moreover, KCTD12 knockdown enhanced tumor growth and metastasis both in vitro and in vivo. Mechanistically, the interaction between KCTD12 and CD271 might be responsible for the stemness transformation after KCTD12 knockdown. CONCLUSIONS: This study identifies for the first time the role of the interaction between KCTD12 and CD271 in inducing melanoma cell stemness transformation. Moreover, KCTD12 repression enhances melanoma cell growth, adhesion, migration and invasion. Chinese Anti-Cancer Association 2019-08 /pmc/articles/PMC6743620/ /pubmed/31565480 http://dx.doi.org/10.20892/j.issn.2095-3941.2019.0073 Text en Copyright 2019 Cancer Biology & Medicine http://creativecommons.org/licenses/by-nc-sa/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-Share Alike 4.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0/
spellingShingle Original Article
Shen, Weiyu
Li, Yumei
Li, Bifei
Zheng, Liping
Xie, Xiaodong
Le, Jingqing
Lu, Yusheng
Li, Tao
Chen, Fan
Jia, Lee
Downregulation of KCTD12 contributes to melanoma stemness by modulating CD271
title Downregulation of KCTD12 contributes to melanoma stemness by modulating CD271
title_full Downregulation of KCTD12 contributes to melanoma stemness by modulating CD271
title_fullStr Downregulation of KCTD12 contributes to melanoma stemness by modulating CD271
title_full_unstemmed Downregulation of KCTD12 contributes to melanoma stemness by modulating CD271
title_short Downregulation of KCTD12 contributes to melanoma stemness by modulating CD271
title_sort downregulation of kctd12 contributes to melanoma stemness by modulating cd271
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6743620/
https://www.ncbi.nlm.nih.gov/pubmed/31565480
http://dx.doi.org/10.20892/j.issn.2095-3941.2019.0073
work_keys_str_mv AT shenweiyu downregulationofkctd12contributestomelanomastemnessbymodulatingcd271
AT liyumei downregulationofkctd12contributestomelanomastemnessbymodulatingcd271
AT libifei downregulationofkctd12contributestomelanomastemnessbymodulatingcd271
AT zhengliping downregulationofkctd12contributestomelanomastemnessbymodulatingcd271
AT xiexiaodong downregulationofkctd12contributestomelanomastemnessbymodulatingcd271
AT lejingqing downregulationofkctd12contributestomelanomastemnessbymodulatingcd271
AT luyusheng downregulationofkctd12contributestomelanomastemnessbymodulatingcd271
AT litao downregulationofkctd12contributestomelanomastemnessbymodulatingcd271
AT chenfan downregulationofkctd12contributestomelanomastemnessbymodulatingcd271
AT jialee downregulationofkctd12contributestomelanomastemnessbymodulatingcd271