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CCBIO Special seminar

CCBIO Special Seminar - Randy Watnick

CCBIO Special Seminar with invited speaker Randolph Watnick from the Department of Surgery, Harvard Medical School and the Vascular Biology Program at Boston Children’s Hospital.

Apart from the interesting talks, the CCBIO seminars are a good way to meet CCBIO members and associates. Please feel free to inform others about this seminar as all are welcome, both to the seminar and to the informal pizza get-together afterwards.

Watnick and Akslen, editors of the new CCBIO book "Biomarkers of the Tumor Microenvironment - Basic Studies and Practical Applications" will be available after the seminar to discuss the book. Registered CCBIO PhD candidates will get a copy of the book (by personal attendance).

Tuesday, December 12, 14.30, at the BBB, Auditorium 1

Speaker: Randolph Watnick from the Department of Surgery, Harvard Medical School and the Vascular Biology Program at Boston Children’s Hospital.

Title: "A novel mechanism governing tumor initiation and cancer stem cell function."

Randolph Watnick is also a CCBIO international affiliated investigator.

Abstract:

The catalog of mutations that drive tumour formation and growth have been extensively studied.  However, despite exhaustive attempts, the functional characterization of the cells, on the molecular level, that give rise to carcinomas, termed tumour-initiating cells is still lacking.

We discovered that the tumor suppressor, p53, is differentially regulated in progenitor-like mammary epithelial cells than in differentiated mammary epithelial cells.  Further investigation revealed that this differential regulation of p53 activity was a function of its acetylation status, as modulated by the deacetylase SIRT1.  We show here that the expression of SIRT1 in mammary epithelial progenitor-like cells is mediated by Notch1.  We then hypothesized that Notch1-mediated regulation of tissue progenitor cells is recapitulated in tumour-initiating cells. Accordingly, we investigated whether the Notch signaling pathway is critical to the tumour-initiating properties of mammary epithelial cells. Strikingly, high Notch1 expression also identifies functional cancer stem cells and Notch-mediated repression of SIRT1 regulates both tumour initiation and chemoresistance.  

These results demonstrate that a novel signaling axis, involving Notch1, SIRT1 and p53 functionally defines tumour-initiating epithelial cells as well as cancer stem cells.