期刊
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
卷 25, 期 19, 页码 9411-9426出版社
WILEY
DOI: 10.1111/jcmm.16883
关键词
Hippo pathway; KCTD11; Wnt pathway; YAP; beta-catenin
资金
- National Natural Science Foundation of China [81401885, 81902986]
- Liaoning Provincial Natural Science Foundation [20180530040]
- Xinjiang Autonomous Region Natural Science Foundation [2020D01A123]
KCTD11 is under-expressed in lung cancer tissues and cells, negatively correlated with differentiation, TNM stage, and lymph node metastasis, and associated with poor prognosis. Overexpression of KCTD11 inhibits proliferation and migration of lung cancer cells by suppressing the Wnt pathway, activating the Hippo pathway, and inhibiting the EMT process.
KCTD11 has been reported to be a potential tumour suppressor in several tumour types. However, the expression of KCTD11 and its role has not been reported in human non-small cell lung cancer (NSCLC). Whether its potential molecular mechanism is related to its BTB domain is also unknown. The expression of KCTD11 in 139 NSCLC tissue samples was detected by immunohistochemistry, and its correlation with clinicopathological factors was analysed. The effect of KCTD11 on the biological behaviour of lung cancer cells was verified in vitro and in vivo. Its effect on the epithelial-mesenchymal transition(EMT)process and the Wnt/beta-catenin and Hippo/YAP pathways were observed by Western blot, dual-luciferase assay, RT-qPCR, immunofluorescence and immunoprecipitation. KCTD11 is under-expressed in lung cancer tissues and cells and was negatively correlated with the degree of differentiation, tumour-node-metastasis (TNM) stage and lymph node metastasis. Low KCTD11 expression was associated with poor prognosis. KCTD11 overexpression inhibited the proliferation and migration of lung cancer cells. Further studies indicated that KCTD11 inhibited the Wnt pathway, activated the Hippo pathway and inhibited EMT processes by inhibiting the nuclear translocation of beta-catenin and YAP. KCTD11 lost its stimulatory effect on the Hippo pathway after knock down of beta-catenin. These findings confirm that KCTD11 inhibits beta-catenin and YAP nuclear translocation as well as the malignant phenotype of lung cancer cells by interacting with beta-catenin. This provides an important experimental basis for the interaction between KCTD11, beta-catenin and YAP, further revealing the link between the Wnt and Hippo pathways.
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