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LKB1 inhibits proliferation, metastasis and angiogenesis of thyroid cancer by upregulating SIK1

Purpose: Liver kinase B1 (LKB1), also known as serine/threonine kinase 11, was considered as a tumor suppressor, which exhibited anti-cancer activity in a variety of cancers. However, the effect of LKB1 in thyroid cancer remains unclear. Methods: In the study, MTT assay, colony formation assay, flow...

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Autores principales: Kou, Bo, Wang, Xin-Di, Sun, Xiao-Peng, Qi, Qin, Yang, Ming, Yun, Yan-Ning, Zhou, Jin-Song, Liu, Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9330453/
https://www.ncbi.nlm.nih.gov/pubmed/35912012
http://dx.doi.org/10.7150/jca.72021
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author Kou, Bo
Wang, Xin-Di
Sun, Xiao-Peng
Qi, Qin
Yang, Ming
Yun, Yan-Ning
Zhou, Jin-Song
Liu, Wei
author_facet Kou, Bo
Wang, Xin-Di
Sun, Xiao-Peng
Qi, Qin
Yang, Ming
Yun, Yan-Ning
Zhou, Jin-Song
Liu, Wei
author_sort Kou, Bo
collection PubMed
description Purpose: Liver kinase B1 (LKB1), also known as serine/threonine kinase 11, was considered as a tumor suppressor, which exhibited anti-cancer activity in a variety of cancers. However, the effect of LKB1 in thyroid cancer remains unclear. Methods: In the study, MTT assay, colony formation assay, flow cytometry, western blot analysis, wound healing assay, transwell assays, quantitative real-time PCR, HUVEC migration assay, ELISA assay, tube formation assay and nude mice xenograft were used to investigate the anti-cancer capacity of LKB1 in thyroid cancer in vitro and in vivo. Results: In the present study, we found that the expression of LKB1 was lower in thyroid cancer tissues and cell lines, compared with the adjacent normal tissue and thyroid epithelial cell. After construction of stable clone cells with ectopic LKB1 overexpression, the findings revealed that LKB1 overexpression exerted anti-proliferative and pro-apoptotic property in thyroid cancer TPC-1 and BCPAP cells. In addition, LKB1 overexpression could inhibit migration and invasion, downregulate MMP2 and MMP9 expressions, and reverse EMT in thyroid cancer cells. Furthermore, overexpression of LKB1 attenuated HUVEC recruitment, decreased the expression of VEGFA and inhibited the formation of new vessels in thyroid cancer cells. To validate the underlying mechanism of LKB1 in thyroid cancer, the results showed that LKB1 could positively regulate SIK1 in thyroid cancer TPC-1 and BCPAP cells. Additionally, the SIK1 inhibitor HG-9-91-01 could partially abrogate the anti-proliferative and anti-metastatic effect of LKB1, and reverse MET (mesenchymal-to-epithelial transition) mediated by LKB1 overexpression. Ultimately, the results in vivo revealed that LKB1 overexpression exhibited a strong inhibitory effect of tumorigenicity and presented anti-angiogenic characteristic in nude mice xenograft model. Conclusion: the results demonstrated that LKB1 could inhibit proliferation, metastasis phenotype and angiogenesis, and reverse EMT in thyroid cancer in vitro and vivo via the upregulation of SIK1, suggesting that LKB1 could be considered as a potential therapeutic target for the treatment of thyroid cancer.
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spelling pubmed-93304532022-07-29 LKB1 inhibits proliferation, metastasis and angiogenesis of thyroid cancer by upregulating SIK1 Kou, Bo Wang, Xin-Di Sun, Xiao-Peng Qi, Qin Yang, Ming Yun, Yan-Ning Zhou, Jin-Song Liu, Wei J Cancer Research Paper Purpose: Liver kinase B1 (LKB1), also known as serine/threonine kinase 11, was considered as a tumor suppressor, which exhibited anti-cancer activity in a variety of cancers. However, the effect of LKB1 in thyroid cancer remains unclear. Methods: In the study, MTT assay, colony formation assay, flow cytometry, western blot analysis, wound healing assay, transwell assays, quantitative real-time PCR, HUVEC migration assay, ELISA assay, tube formation assay and nude mice xenograft were used to investigate the anti-cancer capacity of LKB1 in thyroid cancer in vitro and in vivo. Results: In the present study, we found that the expression of LKB1 was lower in thyroid cancer tissues and cell lines, compared with the adjacent normal tissue and thyroid epithelial cell. After construction of stable clone cells with ectopic LKB1 overexpression, the findings revealed that LKB1 overexpression exerted anti-proliferative and pro-apoptotic property in thyroid cancer TPC-1 and BCPAP cells. In addition, LKB1 overexpression could inhibit migration and invasion, downregulate MMP2 and MMP9 expressions, and reverse EMT in thyroid cancer cells. Furthermore, overexpression of LKB1 attenuated HUVEC recruitment, decreased the expression of VEGFA and inhibited the formation of new vessels in thyroid cancer cells. To validate the underlying mechanism of LKB1 in thyroid cancer, the results showed that LKB1 could positively regulate SIK1 in thyroid cancer TPC-1 and BCPAP cells. Additionally, the SIK1 inhibitor HG-9-91-01 could partially abrogate the anti-proliferative and anti-metastatic effect of LKB1, and reverse MET (mesenchymal-to-epithelial transition) mediated by LKB1 overexpression. Ultimately, the results in vivo revealed that LKB1 overexpression exhibited a strong inhibitory effect of tumorigenicity and presented anti-angiogenic characteristic in nude mice xenograft model. Conclusion: the results demonstrated that LKB1 could inhibit proliferation, metastasis phenotype and angiogenesis, and reverse EMT in thyroid cancer in vitro and vivo via the upregulation of SIK1, suggesting that LKB1 could be considered as a potential therapeutic target for the treatment of thyroid cancer. Ivyspring International Publisher 2022-07-04 /pmc/articles/PMC9330453/ /pubmed/35912012 http://dx.doi.org/10.7150/jca.72021 Text en © The author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
spellingShingle Research Paper
Kou, Bo
Wang, Xin-Di
Sun, Xiao-Peng
Qi, Qin
Yang, Ming
Yun, Yan-Ning
Zhou, Jin-Song
Liu, Wei
LKB1 inhibits proliferation, metastasis and angiogenesis of thyroid cancer by upregulating SIK1
title LKB1 inhibits proliferation, metastasis and angiogenesis of thyroid cancer by upregulating SIK1
title_full LKB1 inhibits proliferation, metastasis and angiogenesis of thyroid cancer by upregulating SIK1
title_fullStr LKB1 inhibits proliferation, metastasis and angiogenesis of thyroid cancer by upregulating SIK1
title_full_unstemmed LKB1 inhibits proliferation, metastasis and angiogenesis of thyroid cancer by upregulating SIK1
title_short LKB1 inhibits proliferation, metastasis and angiogenesis of thyroid cancer by upregulating SIK1
title_sort lkb1 inhibits proliferation, metastasis and angiogenesis of thyroid cancer by upregulating sik1
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9330453/
https://www.ncbi.nlm.nih.gov/pubmed/35912012
http://dx.doi.org/10.7150/jca.72021
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