Cancer stem cells (CSC) maintain both undifferentiated self-renewing CSCs and differentiated, non-self-renewing non-CSCs through cellular division. However, molecular mechanisms that maintain self-renewal in CSCs versus non-CSCs are not yet clear. Here, we report that in a transgenic mouse model of MYC-induced T-cell leukemia, MYC, maintains self-renewal in Sca1 þ CSCs versus Sca-1 À non-CSCs. MYC preferentially bound to the promoter and activated hypoxia-inducible factor-2a (HIF2a) in Sca-1 þ cells only. Furthermore, the reprogramming factors, Nanog and Sox2, facilitated MYC regulation of HIF2a in Sca-1 þ versus Sca-1 À cells. Reduced expression of HIF2a inhibited the self-renewal of Sca-1 þ cells; this effect was blocked through suppression of ROS by N-acetyl cysteine or the knockdown of p53, Nanog, or Sox2. Similar results were seen in ABCG2 þ CSCs versus ABCG2 À non-CSCs from primary human T-cell lymphoma. Thus, MYC maintains self-renewal exclusively in CSCs by selectively binding to the promoter and activating the HIF2a stemness pathway. Identification of this stemness pathway as a unique CSC determinant may have significant therapeutic implications.

BackgroundHuman papilloma virus (HPV) associated Head and Neck Cancers (HNCs) have generated significant amount of research interest in recent times. Due to high incidence of HNCs and lack of sufficient data on high-risk HPV (hr-HPV) infection from North -East region of India, this study was conceived to investigate hr-HPV infection, its types and its association with life style habits such as tobacco, alcohol consumption etc.MethodsA total of one hundred and six primary HNC tumor biopsy specimens were collected. These samples were analyzed for hr-HPV DNA (13 HPV types) using hybrid capture 2 (HC2) assay and genotyping was done by E6 nested multiplex PCR (NMPCR).ResultsThe presence of hr-HPV was confirmed in 31.13% (n = 33) and 24.52% (n = 26) of the HNC patients by nested multiplex PCR (NMPCR) and HC2 assay respectively. Among hr-HPV positive cases, out of thirteen hr- HPV types analyzed, only two prevalent genotypes, HPV-16 (81.81%) followed by HPV-18 (18.18%) were found. Significant association was observed between hr-HPV infection with alcohol consumption (p <0.001) and tobacco chewing (p = 0.02) in HNC cases. Compared to HPV-18 infection the HPV-16 was found to be significantly associated with tobacco chewing (p = 0.02) habit.ConclusionsOur study demonstrated that tobacco chewing and alcohol consumption may act as risk factors for hr-HPV infection in HNCs from the North-East region of India. This was the first study from North-East India which also assessed the clinical applicability of HC2 assay in HNC patient specimens. We suggest that alcohol, tobacco and hr- HPV infection act synergistically or complement each other in the process of HNC development and progression in the present study population.

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