Experimental cell research · 2026
Transcription factor KLF4 inhibits lung cancer cell growth and metastasis by promoting CYLD-induced TEK deubiquitination.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Lu Songmei, Chen Jianbing, Zhang Wei, Chen Jingmei
Аннотация
BACKGROUND: Cylindromatosis (CYLD) has been found to mediate lung cancer (LC) progression as a tumor suppressor, but its related molecular mechanism remains to be further elucidated.
METHODS: The expression of CYLD, Kruppel-like factor 4 (KLF4), and TEK receptor tyrosine kinase (TEK) was analyzed by qRT-PCR or Western blot. The interaction between CYLD and KLF4 or TEK was confirmed using ChIP assay, dual-luciferase reporter assay and Co-IP assay. Cell proliferation, migration, invasion and apoptosis were determined by EdU assay, colony formation assay, transwell assay and flow cytometry. The role of KLF4/CYLD/TEK axis in vivo was further confirmed by constructing mice xenograft models.
RESULTS: CYLD expression was markedly reduced in LC cells and tissues. Transcription factor KLF4 could bind to the promoter region of CYLD to enhance its transcription and expression. KLF4 overexpression repressed LC cell proliferation, migration, invasion and promoted apoptosis, while these effects were abolished by CYLD knockdown. CYLD could increase TEK expression by deubiquitination. The inhibitory effect of CYLD upregulation on LC cell growth and metastasis was reversed by TEK silencing. Animal study showed that overexpression of KLF4 significantly reduced LC tumor growth through activating the CYLD/TEK axis.
CONCLUSION: KLF4-activated CYLD repressed LC cell growth and metastasis by increasing TEK deubiquitination, providing a new regulatory axis for the development of LC potential molecular targets.
METHODS: The expression of CYLD, Kruppel-like factor 4 (KLF4), and TEK receptor tyrosine kinase (TEK) was analyzed by qRT-PCR or Western blot. The interaction between CYLD and KLF4 or TEK was confirmed using ChIP assay, dual-luciferase reporter assay and Co-IP assay. Cell proliferation, migration, invasion and apoptosis were determined by EdU assay, colony formation assay, transwell assay and flow cytometry. The role of KLF4/CYLD/TEK axis in vivo was further confirmed by constructing mice xenograft models.
RESULTS: CYLD expression was markedly reduced in LC cells and tissues. Transcription factor KLF4 could bind to the promoter region of CYLD to enhance its transcription and expression. KLF4 overexpression repressed LC cell proliferation, migration, invasion and promoted apoptosis, while these effects were abolished by CYLD knockdown. CYLD could increase TEK expression by deubiquitination. The inhibitory effect of CYLD upregulation on LC cell growth and metastasis was reversed by TEK silencing. Animal study showed that overexpression of KLF4 significantly reduced LC tumor growth through activating the CYLD/TEK axis.
CONCLUSION: KLF4-activated CYLD repressed LC cell growth and metastasis by increasing TEK deubiquitination, providing a new regulatory axis for the development of LC potential molecular targets.