Title : Epithelial stem cells and cancer
Abstract:
The skin is maintained by self-renewal, proliferation, and differentiation of tissue-specific stem cells. We have shown previously that the transcription factor p63 plays an essential role in these processes. Although p63 has high sequence and structural similarities to the tumor suppressor p53, it is rarely mutated in human cancers. Unlike p53, however, p63 is frequently upregulated in various epithelial cancers, leading to the current working hypothesis in the field that p63 plays predominantly an oncogenic role when it is overexpressed. However, transgenic mice overexpressing p63 do not produce spontaneous tumors, raising the possibility that an alterative mechanism of p63 exists in cancer development. By creating a novel mouse model of p63 mutant, we discovered that aberrant splicing of p63 sensitizes the epithelial stem cells to tumorigenesis. Notably, we found that the same splicing mutant of p63 collaborates with the oncogenic signalling, leading to the formation of squamous cell carcinoma of epithelia. Collectively, our data show that aberrant p63 splicing contributes to the development of squamous cell carcinoma. We will also discuss newly identified mechanisms of cancer in the other epithelial organs. In sum, our data establish p63 as the key molecule that drives epithelial tumorigenesis.
Audience Take Away Notes:
- This helps us to learn about the history of the p63-associated human cancers.
- It helps us to learn about the p63-asociated novel mechanism of squamous carcinoma.
- This also helps us to learn about the other epithelial cancers that are induced by aberrant p63 expression
