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Spontaneous Murine Model of Anaplastic Thyroid Cancer
Published on: February 3, 2023
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BUB1/KIF14 complex promotes anaplastic thyroid carcinoma progression by inducing chromosome instability
Tiefeng Jin1, Lingling Ding1, Jinming Chen2
1Otolaryngology & Head and Neck Center, Cancer Center, Department of Head and Neck Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, China.
Journal of Cellular and Molecular Medicine
|March 18, 2024
Summary
Chromosome instability drives anaplastic thyroid cancer (ATC). The BUB1 kinase promotes ATC aggressiveness by inducing chromosome instability via KIF14 phosphorylation, making BUB1 a potential therapeutic target for ATC.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Chromosome instability (CIN) is a known driver of anaplastic thyroid cancer (ATC) progression.
- The role of BUB1 mitotic checkpoint serine/threonine kinase (BUB1) in ATC pathogenesis is not well understood.
Purpose of the Study:
- To investigate the role of BUB1 in ATC development and progression.
- To elucidate the underlying molecular mechanisms by which BUB1 influences ATC aggressiveness.
Main Methods:
- Analysis of BUB1 expression in ATC samples and correlation with patient survival.
- In vitro studies involving BUB1 knockdown and overexpression in ATC and papillary thyroid cancer cells.
- In vivo studies using nude mice xenografts and zebrafish models to assess tumor growth and metastasis.
- Investigation of BUB1's interaction with KIF14 and its phosphorylation at Serine 1292.
Main Results:
- BUB1 is significantly upregulated in ATC and associated with poorer progression-free survival.
- BUB1 inhibition reduces ATC cell viability, invasion, migration, and induces cell cycle arrest.
- BUB1 knockdown suppresses tumor growth and metastasis in vivo.
- BUB1 induces CIN in ATC cells by phosphorylating KIF14 at Ser1292, promoting cancer aggressiveness.
Conclusions:
- The BUB1/KIF14 complex is a key driver of ATC aggressiveness through the induction of CIN.
- Targeting BUB1, potentially with inhibitors like BAY-1816032, shows therapeutic potential for ATC.
Keywords:
BUB1 mitotic checkpoint serine/threonine kinaseanaplastic thyroid carcinomachromosome instabilityphosphorylationproliferationMore Related Videos
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