Dataset Information

CDK1 Promotes Epithelial-Mesenchymal Transition and Migration of Head and Neck Squamous Carcinoma Cells by Repressing ∆Np63α-Mediated Transcriptional Regulation.

ABSTRACT: ∆Np63α is a key transcription factor overexpressed in types of squamous cell carcinomas (SCCs), which represses epithelial-mesenchymal transition (EMT) and cell migration. In this study, we found that CDK1 phosphorylates ∆Np63α at the T123 site, impairing its affinity to the target promoters of its downstream genes and its regulation of them in turn. Database analysis revealed that CDK1 is overexpressed in head and neck squamous cell carcinomas (HNSCCs), especially the metastatic HNSCCs, and is negatively correlated with overall survival. We further found that CDK1 promotes the EMT and migration of HNSCC cells by inhibiting ∆Np63α. Altogether, our study identified CDK1 as a novel regulator of ΔNp63α, which can modulate EMT and cell migration in HNSCCs. Our findings will help to elucidate the migration mechanism of HNSCC cells.

SUBMITTER: Chen H

PROVIDER: S-EPMC9266818 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

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CDK1 Promotes Epithelial-Mesenchymal Transition and Migration of Head and Neck Squamous Carcinoma Cells by Repressing ∆Np63α-Mediated Transcriptional Regulation.

Chen Huimin H Hu Ke K Xie Ying Y Qi Yucheng Y Li Wenjuan W He Yaohui Y Fan Shijie S Liu Wen W Li Chenghua C

International journal of molecular sciences 20220702 13

∆Np63α is a key transcription factor overexpressed in types of squamous cell carcinomas (SCCs), which represses epithelial-mesenchymal transition (EMT) and cell migration. In this study, we found that CDK1 phosphorylates ∆Np63α at the T123 site, impairing its affinity to the target promoters of its downstream genes and its regulation of them in turn. Database analysis revealed that CDK1 is overexpressed in head and neck squamous cell carcinomas (HNSCCs), especially the metastatic HNSCCs, and is ...[more]

PMID: 35806389

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Project description:Initiation, growth, recurrence, and metastasis of head and neck squamous cell carcinomas (HNSCC) have been related to the behavior of cancer stem cells (CSC) that can be identified by their aldehyde-dehydrogenase-isoform-1 (ALDH1) activity. We quantified and enriched ALDH1(+) cells within HNSCC cell lines and subsequently characterized their phenotypical and functional properties like invasion capacity and epithelial-mesenchymal transition (EMT). Spheroid culture enriched CSC from five HNSCC cell lines by up to 5-fold. In spheroid-derived cells (SDC) and the parental monolayer-derived cell line ALDH1, CD44, CD24, E-Cadherin, α-SMA, and Vimentin expression was compared by flow-cytometry and immunofluorescence together with proliferation and cell cycle analysis. Invasion activity was evaluated by Matrigel assay and expression of stemness-related transcription factors (TF) Nanog, Oct3/4, Sox2 and EMT-related genes Snail1 and 2, and Twist by real-time PCR. All cell lines formed spheroids that could self-renew and be serially re-passaged. ALDH1 expression was significantly higher in SDC. ALDH1(+) cells showed increased colony-formation. The proportion of cells with a putative CSC marker constellation of CD44(+)/CD24(-) was highly variable (0.5% to 96%) in monolayer and spheroid cultures and overlapped in 0%-33% with the CD44(+)/CD24(-)/ALDH1(+) cell subset. SDC had significantly higher invading activity. mRNA of the stemness-related genes Sox2, Nanog, and Oct3/4 was significantly increased in SDC of all cell lines. Twist was significantly increased in two while Snail2 showed a significant increase in one and a significant decrease in SDC of two cell lines. SDC had a higher G0 phase proportion, showed high-level expression of α-SMA and Vimentin, but significantly decreased E-Cadherin expression. HNSCC-lines harbor potential CSC, characterized by ALDH1 and stemness marker TF expression as well as properties like invasiveness, quiescence, and EMT. CSC can be enriched by anchorage-independent culture techniques, which may be important for the investigation of their contribution to therapy resistance, tumor recurrence and metastasis.

Dataset Information

CDK1 Promotes Epithelial-Mesenchymal Transition and Migration of Head and Neck Squamous Carcinoma Cells by Repressing ∆Np63α-Mediated Transcriptional Regulation.

Publications

CDK1 Promotes Epithelial-Mesenchymal Transition and Migration of Head and Neck Squamous Carcinoma Cells by Repressing ∆Np63α-Mediated Transcriptional Regulation.

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