Seminar "Generating, characterizing and targeting breast cancer stem cells."

Cell Signal Unit (Yamamoto Unit) would like to invite you to a seminar by Dr. Guillaume Varès.

We look forward to your participation.

Speaker: Dr. Guillaume Varès

Research Center for Radiation Protection, National Institute of Radiological Sciences

Title: Generating, characterizing and targeting breast cancer stem cells

Abstract: Basal-like breast cancer (BBC) is of particular concern, due to its high frequency, lack of effective therapies and poor prognosis. Ionizing radiation and cumulative exposure to steroid hormones are known risk factors for breast cancer. Because of their tumor-initiating properties, cancer stem cells (CSCs) were proposed to be responsible for relapse and metastasis. We have shown that progesterone (P4) might influence radiation-induced breast cancer risk by generating tumor-initiating breast cancer stem cells in normal and breast cancer cells. In MCF10A non-cancerous basal-like PR-negative cells, P4 and X-rays triggered cancer and stemness-associated microRNA regulations and generated ALDH+ and CD44+/CD24- radiation-resistant tumor-initiating CSCs. P4 activated the Pi3k/Akt pathway via membrane progesterone receptor (mPR), resulting in the inactivation of FOXO transcriptional activity, the upregulation of snail and slug expression and a downregulation of miR-29 expression, which led to increased levels of KLF4, a transcription factor required for breast CSC maintenance. Stabilization of miR-29 expression impeded the generation of CSCs, while its inhibition alone was sufficient to generate CSCs. The elucidation of new pathways and miRNA regulations involved in basal-like CSC maintenance may open the door to new strategies for BBC primary or adjuvant therapy, which may be effective at preventing metastasis and relapse. The relevance of such strategies for other challenging cancer models will also be discussed.

Host: 

Tadashi Yamamoto, Cell Signal Unit