p53 Family, Oncogenic Signaling and Cancer Metastasis

Inactivation of the tumor suppressor protein p53 plays a critical role in tumorigenesis, whereas p53-related p63 gene is essential in epithelial development and stem cell biology. Emerging evidence indicates that mutant p53 proteins acquire gain of functions in promoting cancer metastasis and that p63 is important in regulation of cell migration/invasion. We have recently shown a novel pathway with which the p53 hotspot point mutant, p53-R273H, in promoting cancer metastasis. In addition, we have demonstrated that p63 modulates ERK signaling in regulating cell migration/invasion. Our recent studies also indicate an essential role for p63 in mediating PI3K-induced cancer progression.

References:

1. J Bergholz1, Y Zhang, J Wu, L Meng, EM Walsh, A Rai, MY Sherman and Z-X Xiao*.(2014) ΔNp63α regulates Erk signaling via MKP3 to inhibit cancer metastasis. Oncogene 33, 212–224.
2. Junfeng Wu, Shan Liang, Johann Bergholz, Hanbing He, Erica M. Walsh, Yujun Zhang, Zhi-Xiong Xiao* (2014) ΔNp63α activates CD82 metastasis suppressor to inhibit cancer cell invasion. Cell Death and Disease 5, e1280; doi:10.1038/cddis.2014.239
3. Chenghua Li, Donny L.F.Chang, Zemin Yang, Jin Qi, Ruihong Liu, Hanbing He, Decai Li, Zhi-Xion Xiao* (2013) Pin1 modulates ΔNp63α protein stability in regulation of cell survival, proliferation and tumor formation. Cell Death and Disease 4, e943; doi:10.1038/cddis.2013.468.
4. Johann Bergholz and Zhi-Xiong Xiao*, (2012) Role of p63 in Development, Tumorigenesis and Cancer Progression. Cancer Microenvironment 5:311–322.