Y-box Binding Protein-1 Is Part of a Complex Molecular Network Linking Np63 to the PI3K/akt Pathway in Cutaneous Squamous Cell Carcinoma

Cutaneous squamous cell carcinomas (SCCs) typically lack somatic oncogene-activating mutations and most of them contain p53 mutations. However, the presence of p53 mutations in skin premalignant lesions suggests that these represent early events during tumor progression and additional alterations may be required for SCC development. SCC cells frequently express high levels of Np63 and Y-box binding 1 (YB-1 or YBX1) oncoproteins. Here, we show that knockdown of YB-1 in spontaneously immortalized HaCaT and non-metastatic SCC011 cells led to a dramatic decrease of Np63, cell detachment and death. In highly metastatic SCC022 cells, instead, YB-1 silencing induces PI3K/AKT signaling hyperactivation which counteracts the effect of YB-1 depletion and promotes cell survival. In summary, our results unveil a functional cross-talk between YB-1, Np63 and the PI3K/AKT pathway critically governing survival of squamous carcinoma cells. J. Cell. Physiol. 230: 2067-2074, 2015. (c) 2015 Wiley Periodicals, Inc.