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Background  ΔNp63, a splice variant of p63, is overexpressed and exhibits oncogenic activity in many cancers including pancreatic and breast cancer and promotes cell survival by inhibiting apoptosis. Despite its role in tumorigenesis, mechanistic activity of ΔNp63 mediated oncogenic function in osteosarcoma is poorly understood.    Methods  The expression levels of p63 isoforms in osteosarcoma cell lines were identified using quantitative techniques. Expression profiling using microarray, siRNA mediated loss-of-function, and chromatin immunoprecipitation assays were employed to identify novel ΔNp63α targets in  p63 -null osteosarcoma SaOS-2 cells that were engineered to express ΔNp63α. The phenotype of SaOS-2-ΔNp63α cells was assessed using wound-healing, colony formation, and proliferation assays.    Results  The comparative expression analyses identified ΔNp63α as the predominant p63 isoform expressed by invasive OS cell lines. Phenotypic analyses of SaOS-2-ΔNp63α cells  in vitro  indicate that ΔNp63α imparted tumorigenic attributes upon tumor cells. Further, we show that in osteosarcoma cells ΔNp63α directly regulated the transcription factor  GLI2 , which is a component of the hedgehog signaling pathway, and that functional interactions between ΔNp63α and  GLI2  confer oncogenic properties upon OS cells.    Conclusions  Here, we report that  GLI2  is the novel target gene of ΔNp63α and that ΔNp63α- GLI2  crosstalk in osteosarcoma cells is a necessary event in osteosarcoma progression. Defining the exact mechanisms involved in this interaction that mediate the pathogenesis of osteosarcoma promises to identify targets for drug therapy.    Electronic supplementary material  The online version of this article (doi:10.1186/1471-2407-14-559) contains supplementary material, which is available to authorized users.

ΔNp63α enhances the oncogenic phenotype of osteosarcoma cells by inducing the expression of GLI2