KCTD11 inhibits progression of lung cancer by binding to β-catenin to regulate the activity of the Wnt and Hippo pathways

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/β-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 β-catenin and YAP. KCTD11 lost its stimulatory effect on the Hippo pathway after knock down of β-catenin. These findings confirm that KCTD11 inhibits β-catenin and YAP nuclear translocation as well as the malignant phenotype of lung cancer cells by interacting with β-catenin. This provides an important experimental basis for the interaction between KCTD11, β-catenin and YAP, further revealing the link between the Wnt and Hippo pathways.     

The Hippo pathway: a renewed insight in the craniofacial diseases and hard tissue remodeling

The Hippo pathway plays an important role in many pathophysiological processes, including cell proliferation and differentiation, cell death, cell migration and invasion. Because of its extensive functions, Hippo pathway is closely related to not only growth and development, but also many diseases, including inflammation and cancer. In this study, the role of Hippo pathway in craniofacial diseases and hard tissue remodeling was reviewed, in attempting to find new research directions.     

Interferon-γ induces tumor resistance to anti-PD-1 immunotherapy by promoting YAP phase separation

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慢病毒siRNA靶向干扰YAP基因胃癌细胞株的建立

目的：构建并鉴定YAP基因短发夹干扰RNA（shRNA）慢病毒载体,建立稳定干扰YAP基因表达的胃癌细胞株SGC7901。方法：荧光定量PCR检测YAP基因在多种胃癌细胞株中的表达情况。构建重组靶向YAP基因的shRNA慢病毒表达质粒PGC-shRNA-YAP,用脂质体转染的方法将载体导入胃癌细胞。经杀稻瘟菌素筛选后,建立稳定表达siRNA的细胞株。荧光定量PCR检测干扰效率。结果：在胃癌细胞株SGC7901中,YAP基因显示高表达。测序验证PGC-shRNA-YAP重组质粒构建成功。将重组质粒稳定转染入胃癌细胞株SGC7901后能明显抑制YAPmRNA表达水平。结论：成功构建了PGC-shRNA-YAP慢病毒重组质粒,建立了靶向稳定干扰YAP基因表达的siRNA胃癌细胞株SGC7901。     

Aberrant Kank1 expression regulates YAP to promote apoptosis and inhibit proliferation in OSCC

The kidney ankyrin repeat-containing protein 1 (Kank1) gene is one of the most important members of the KANK family. Kank1 has hybridity deletion and promoter methylation in the cancer tissues of the brain, lung, kidney and the corresponding cell lines, leading to downregulation of the gene expression. Meanwhile, Kank1 also plays a key role in the occurrence and development of various types of tumors, suggesting that Kank1 may be an anti-oncogene. However, its role and the potential mechanisms in the Oral Squamous Cell Carcinoma (OSCC) remain unclear. We examined the expression of Kank1 in OSCC tissues and explored its clinical significance. In addition, we investigated the effects of Kank1 on the biological behavior of OSCC cells and their specific molecular mechanisms. We found that Kank1 was poorly expressed in OSCC tissues and it is correlated with the OSCC stage and the patient's poor prognosis. By overexpression of Kank1, we found that the proliferation ability of the OSCC cells decreased both in vitro and in vivo, the proportion of apoptotic cells increased, and the mitochondrial transmembrane potential decreased. In terms of the molecular mechanism, we confirmed that Kank1 could inhibit the occurrence of OSCC by regulating Yap to inhibit the proliferation and promote apoptosis of the OSCC cells. Moreover, it was found that the overexpression of YAP reversed those effects caused by Kank1 overexpression on the OSCC cells. In conclusion, the research indicated that Kank1 might play an anti-oncogenic role in OSCC and it could be considered to be a target for the diagnosis and the treatment of OSCC.