E3-ligase Skp2 predicts poor prognosis and maintains cancer stem cell pool in nasopharyngeal carcinoma
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Jing Wang1,2,*, Ying Huang1,*, Zhong Guan3,*, Jia-liang Zhang3,*, Hong-kai Su1, Wei Zhang1,2, Cai-feng Yue1,2, Min Yan1,2, Su Guan4 and Quentin Qiang Liu1,2
1 State key laboratory of oncology in South China, Collaborative Innovation Center of Cancer Medicine, Department of Research Laboratory, Sun Yat-sen University Cancer Center, Guangzhou, China
2 Department of Research Laboratory, Sun Yat-sen University Cancer Center, Guangzhou, China
3 Department of Otorhinolaryngology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
4 School of Bioscience and Biotechnology, South China University of Technology, Guangzhou, China
* These authors contribute equally to this work
Jing Wang, email:
Quentin Qiang Liu, email:
Keywords: S-phase kinase associated protein 2 (Skp2), nasopharyngeal carcinoma (NPC), aldehyde dehydrogenase1 (ALDH1), cancer stem cell (CSC)
Received: March 24, 2014 Accepted: June 29, 2014 Published: June 30, 2014
Nasopharyngeal carcinoma (NPC) is one of the severe head and neck carcinomas, which is rare in west countries but has high incidence in Southern Asia especially South China. Although NPC is relatively sensitive to radiotherapy, the prognosis of patients is poor due to the advanced stage at the time of diagnosis. Therefore, it is important to understand the mechanisms involved in tumorigenesis and develop early diagnostic techniques. S-phase kinase associated protein 2 (Skp2) is overexpressed in several human cancers and associates with poor prognosis. However, its function in NPC has not been fully addressed. In this study we found Skp2 was highly expressed in NPC specimen and correlated with poor prognosis. We generated Skp2 knockdown cells to further delineate its role in NPC development. Knockdown of Skp2 partially reduced cell proliferation, promoted cellular senescence, and decreased the population of stem cell like aldehyde dehydrogenase1 positive cells as well as their self-renewal ability. Our study not only interprets the predictive role of Skp2 in the poor prognosis of NPC patients, but also reveals that Skp2 regulates the NPC cancer stem cell maintenance, which shed lights on the target therapy and early diagnosis of NPC in clinical application.
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