Oncogenic activity may be key to carcinoma development

Keyes WM. Cell Stem Cell. 2011;doi:10.1016/j.stem.2010.12.009.

An oncogene in the skin, known as ΔNp63α, may inhibit oncogene-induced senescence and stimulate stem cells that produce keratin 15, according to recent findings.

Researchers from several sites worldwide hypothesized that because p63 deficiency induces cellular senescence, it may also be involved in tumor suppressive activity. They coinfected primary keratinocytes of mice with Ras and expression constructs encoding ΔNp63α, Tap63a or a mutant form of ΔNp63α, ΔNp63α ^R279H.

Results indicated that the oncogene ΔNp63α may promote stem-like proliferation and carcinoma. The oncogene may also inhibit oncogene-induced senescence, which could, in turn, shed light on the mechanism that explains why overexpression of this isoform in tumors is an early event with substantial penetration.

Bypass of senescence may be assisted by Lsh, a chromatin remodeler of the SNF2 family. The researchers also observed that “bypass of senescence promotes stem-like proliferation and maintains survival of the keratin 15-positive stem cell population,” according to the results.

“These findings indicate that ΔNp63α is an oncogene that cooperates with Ras to promote tumor-initiating stem-like proliferation and suggest that Lsh-mediated chromatin-remodeling events are critical to this process,” the researchers wrote.

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