Abstract
BackgroundOctamer-binding transcription factor 4A (OCT4A) is essential for cell pluripotency and reprogramming both in humans and mice. To date, however, the function of human OCT4 in somatic and/or tumour tissues is largely unknown.MethodsRT-PCR was used to identify full-length splice forms of OCT4 transcripts in normal and cancer cells. A FLAG-tagged OCT4 genomic transgene was used to identify OCT4-positive cancer cells. A potential role for OCT4 in somatic cancer cells was examined by cell ablation of OCT4-positive cells using promoter-driven diphtheria toxin A. OCT4 and secreted phosphoprotein 1 (SPP1) transcripts in early-stage lung adenocarcinoma tumours were analysed and compared with pathohistological features.ResultsThe results show that, unlike in murine cells, OCT4A and OCT4B variants are transcribed in both human cancer cells and in adult tissues such as lung, kidney, uterus, breast, and eye. We found that OCT4A and SPP1C are co-expressed in highly aggressive human breast, endometrial, and lung adenocarcinoma cell lines, but not in mesothelial tumour cell lines. Ablation of OCT4-positive cells in lung adenocarcinoma cells significantly decreased cell migration and SPP1C mRNA levels. The OCT4A/SPP1C axis was found in primary, early-stage, lung adenocarcinoma tumours.ConclusionsCo-expression of OCT4 and SPP1 may correlate with cancer aggressiveness, and the OCT4A/SPP1C axis may help identify early-stage high-risk patients with lung adenocarcinoma. Contrary to the case in mice, our data strongly suggest a critical role for OCT4A and SPP1C in the development and progression of human epithelial cancers.
Highlights
Octamer-binding transcription factor 4A (OCT4A) is essential for cell pluripotency and reprogramming both in humans and mice
octamer-binding transcription factor 4A (OCT4)-transcript variants are expressed in human somatic tissues at lower levels than in PA-1, a human ovarian teratocarcinoma cell line We examined the expression of OCT4-transcript variants in 24 commercially available RNA samples from human tissues and cells using highly specific primer sets [16]
To confirm a potential role for OCT4A and OCT4Bv (B-splice variants save for OCT4Bns) in the aggressiveness of human somatic cancers, we examined the expression of OCT4 transcripts in breast and various lung tumour cell lines (Fig. 2b and c)
Summary
Octamer-binding transcription factor 4A (OCT4A) is essential for cell pluripotency and reprogramming both in humans and mice. OCT3A and OCT3/4A) is crucial for cell pluripotency in early embryonic development and propagation of the mammalian germline [5,6,7,8,9] It is a marker for germ-cell tumours and a potential CSCs marker [6, 10]. Another study reported the identification of CSC-like phenotype by OCT4 promoter mediated activity in an osteosarcoma cell line [13]. These studies suggest that OCT4 plays an role in human somatic cancers, its somatic function is controversial. Previous studies indicated that OCT4A does not play a functional role in adult somatic murine tissues [17, 18], many researchers have been reticent to accept a role for OCT4A in human adult somatic tissues or related cancers [14, 18,19,20,21,22]
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