Aberrant Kank1 expression regulates YAP to promote apoptosis and inhibit proliferation in OSCC. Issue 2 (23rd July 2019)

• Record Type: Journal Article
• Authors: Fan, Hui; Tian, Hao; Cheng, Xiang; Chen, Yanan; Liang, Shoujian; Zhang, Zhenjian; Liao, Yong; Xu, Pu
• Is Part Of: Journal of cellular physiology. Volume 235:Issue 2(2020:Feb.)
• Page Start: 1850
• Page End: 1865
• Publication Date: 2019-07-23
• Subjects: anti‐oncogenic -- Kank1 -- OSCC -- YAP; Physiology -- Periodicals; Cell physiology -- Periodicals; 571.6
• DOI: 10.1002/jcp.29102
• Languages: English
• ISSNs: 0021-9541

Abstract

Abstract: 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. Abstract : Our research revealed that the low expression of Kidney ankyrin repeat‐containing protein 1 (Kank1) in the Oral Squamous Cell Carcinoma (OSCC) tissue might be because of the inhibition of Kank1 gene expression caused by Kank1 promoter methylation, and its low expression was associated with the OSCC stage and poor prognosis of patients. Meanwhile, it is found that Kank1 might inhibit the proliferation of OSCC cells, promote the apoptosis via the molecular mechanism of promoting the apoptosis of OSCC cells through regulating the YAP signaling pathway by Kank1, thereby inhibiting the occurrence of OSCC. We believed that Kank1 might be a predictor of the survival and prognosis of patients with OSCC, and it could provide new and effective ideas for clinical diagnosis and treatment decision‐making of OSCC.