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Abstract
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.
Highlights
Nasopharyngeal carcinoma (NPC) is one of the most common head and neck cancers in Southern Asia and Northern Africa, the incidence reaches 25 per 100,000 people which is only 0.5~2 per 100,000 people in European and American [1]
We demonstrate that S-phase kinase-associated protein 2 (Skp2) is a potential poor prognosis marker for NPC patients, inactivation of Skp2 decreases the NPC Cancer stem cells (CSCs) population as well as their self-renewal ability
Skp2 high expression was examined in 42.1% (40/95) and low expression was examined in 57.9% patients (55/95)
Summary
Nasopharyngeal carcinoma (NPC) is one of the most common head and neck cancers in Southern Asia and Northern Africa, the incidence reaches 25 per 100,000 people which is only 0.5~2 per 100,000 people in European and American [1]. Diagnosis is important for NPC patients since it is sensitive to radiotherapy at the early stage. About 30% to 40% of NPC patients were diagnosed at advanced stage, which are not response well to treatments and will develop metastasis or recurrence at an average of 4 years. S-phase kinase-associated protein 2 (Skp2), a member of F-box protein family, is the substrate recognition subunit of Skp1-Cullin-F box protein (SCF) E3 ubiquitin ligase complex [2]. Skp is overexpressed and associated with poor prognosis in variety of human cancers, including prostate cancer [4], gastric cancer[5], breast cancer [6, 7], and liver cancer [8], www.impactjournals.com/oncotarget patients (n = 95)
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