Cancer stem cells (CSCs) have been suggested as responsible for the initiation and progression of cancers. Octamer-binding transcription factor 4 (Oct4) is an important regulator of embryonic stem cell fate. Here, we investigated whether Oct4 regulates stemness of head and neck squamous carcinoma (HNSC) CSCs. Our study showed that ectopic expression of Oct4 promotes tumor growth through cyclin E activation, increases chemoresistance through ABCC6 expression and enhances tumor invasion through slug expression. Also, Oct4 dedifferentiates differentiated HNSC cells to CSC-like cells. Furthermore, Oct4high HNSC CSCs have more stem cell-like traits compared with Oct4low cells, such as self-renewal, stem cell markers' expression, chemoresistance, invasion capacity and xenograft tumorigeneity in vitro and in vivo. In addition, knockdown of Oct4 led to markedly lower HNSC CSC stemness. Finally, there was a significant correlation between Oct4 expression and survival of 119 HNSC patients. Collectively, these data suggest that Oct4 may be a critical regulator of HNSC CSCs and its targeting may be potentially valuable in the treatment of HNSC CSCs.
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This work was supported by a grant of the Korean Health Technology R&D Project, Ministry of Health and Welfare, Republic of Korea (Grant number A111700 to YCL) and by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MEST) (Grant number 2012R1A2A2A01046214 to YCL and 2013R1A2A2A01015281 to BSK).
The authors declare no conflict of interest.
Supplementary Information accompanies this paper on the Oncogene website
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Koo, B., Lee, S., Kim, J. et al. Oct4 is a critical regulator of stemness in head and neck squamous carcinoma cells. Oncogene 34, 2317–2324 (2015) doi:10.1038/onc.2014.174
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