LIST OF SELECTED PUBLICATIONS
NEWS FROM THIS GROUP
CONVERSATIONS WITH KEY FIGURES IN MAMMARY GLAND BIOLOGY AND CANCER
BASEL BREAST CONSORTIUM
EU-LIFE TRANSLATIONAL WORKING GP
Molecular mechanisms controlling normal and neoplastic breast stem cells, metastasis and resistanceEach year 1.4 million cases of breast cancer will occur among women worldwide and 450,000 women will die from this disease, mostly due to metastasis. Although progress has been made in broadly understanding breast cancer biology, most of the relevant molecules and signaling pathways remain undefined.
Since starting our research group in November 2006, we have successfully addressed key questions in the fields of normal and neoplastic breast stem cells, metastasis, and resistance to targeted therapies at the molecular, cellular, and whole organism levels. We are currently using and will continue to use systems medicine quantitative methods, unbiased pooled shRNA or transposon-based screens, and hypotheses-driven approaches to study these important areas.
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. And we have already been successful in addressing some of these questions (24 research papers, 16 reviews/commentaries and 8 patents in just 8 years). These scientific achievements include:
- Discovery of key effects 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., Oncogene, 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, Drug Resist Updat, and 2 patents).
- Interruption of anti-CCL2 treatment leads to an overshoot of metastases
A paradoxical effect of the chemokine CCL2 in metastatic breast cancer. While CCL2 neutralization in mouse models inhibits metastasis, subsequent interruption of CCL2 inhibition leads to an overshoot of metastatic load and accelerates the death of the animals. We have elucidated the underlying cellular and molecular mechanisms (Bonapace et al., Nature).
- 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 and Trends Mol Med).
- The identification and validation of the effects of PTP1B, PTPα, PTP-PEST, delta-HER2 and ANO1 in breast cancer (please see selected publication list).
- Novel technologies and model systems
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 (Duss et al., BCR), 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 and Nature).
Two-photon image of a tumor (green) with blood vessels and monocytes (red).
FMI report pages for Mohamed Bentires-Alj