Molecular mechanisms controlling normal and neoplastic breast stem cells, metastasis and resistanceEach year 1.1 million new cases of breast cancer occur among women worldwide and 450,000 women die from this disease. In most cases, metastasis is the cause of death. Although progress has been made in broadly understanding breast tumor biology and progression to metastases, most of the relevant molecules and pathways remain undefined.
The goal of our research is to understand the fundamental molecular mechanisms controlling normal and neoplastic breast stem cells, metastasis and resistance to targeted therapy.
We have developed novel technologies and original tools to study the molecular mechanisms of stem cells, metastasis and resistance. These include novel 3D culture conditions of human breast epithelial cells, invasive 3D cultures of transformed breast cells (Aceto et al BCR; Alajati et al, Cancer Res), conditional knockouts and transgenic mice (Meyer et al, Cancer Res; Koren S FEBS J), primary derived xenograft models of breast cancer and a multiphoton intravital microscope for studying tumor stroma interactions and metastasis in 4D and at a single-cell level (Bonapace et al, JMGBN).
Fully equipped and well positioned
Our laboratory is fully equipped and is well positioned to address key fundamental and unsolved questions in the fields of breast stem cells, metastasis and resistance at the molecular, cellular and whole organism levels. And we have already been successful in addressing some of these questions (16 research papers, 11 reviews/commentaries and 7 patents in just 6 years). These scientific achievements include:
- Discovery of key role for SHP2 in breast cancer stem cells
The discovery of a key role for SHP2 in breast cancer stem cells and validation of this phosphatase as a target in metastatic breast cancer (Aceto et al, Nat Med, Sausgruber et al, submitted, and 2 patents).
- IL8/JAK2-evoked feedback loop interfering with PI3K/mTOR inhibition
The discovery of an IL8/JAK2-evoked positive feedback loop that dampens the efficacy of PI3K/mTOR inhibition. Our results provide a rationale for combined targeting of the PI3K/mTOR and JAK2 pathways in triple-negative breast cancer, a particularly aggressive and currently incurable disease (Britschgi et al, Cancer Cell, and 2 patents).
- Effects of early pregnancy on mammary epithelial cell fate
The finding that parity induces differentiation and reduces proliferation potential and Wnt/Notch signaling ratio in mouse mammary stem/progenitor cells, thus elucidating the cellular and molecular mechanisms underlying the protective effect of an early full-term pregnancy (Meier-Abt et al, BCR).
- The identification and validation of the effects of PTP1B, PTPα, PTP-PEST, delta-HER2 and ANO1 in breast cancer (please see selected publication list).
Images of co-cultures of human mammary epithelial cells and stroma.
FMI report pages for Mohamed Bentires-Alj