Mohamed (Momo) Bentires-Alj

Institution: Department of Biomedicine, University Hospital Basel

Address:

Hebelstrasse 20
CH-4031 Basel / Switzerland

Email: m.bentires-alj@unibas.ch

Group website: biomedizin.unibas.ch/research/research-group-details/home/researchgroup/tumor-heterogeneity-metastasis-and-resistance/

Phone: +41 61 265 33 13

Research interests:

Molecular mechanisms controlling normal and neoplastic breast stem cells, metastasis and resistance
Each 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.

Novel technologies
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. 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, Britschgi et al, Drug Res Updates, 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 and Meier-Abt and bentires-Alj, Trends Molec Med).
  • The identification and validation of the effects of PTP1B, PTPα, PTP-PEST, delta-HER2 and ANO1 in breast cancer.

Selected publications:

Meyer DS, Aceto N, Sausgruber N, Brinkhaus H, Müller U, Pallen CJ, Bentires-Alj M. Tyrosine phosphatase PTPα contributes to HER2-evoked breast tumor initiation and maintenance. Oncogene. 2014 Jan 16;33(3):398-402.

Alajati A, Sausgruber N, Aceto N, Duss S, Sarret S, Voshol H, Bonenfant D, Bentires-Alj M. (2013) Mammary tumor formation and metastasis evoked by a HER2 splice variant. Cancer Res, 2013 Jul 18. [Epub ahead of print]

Meier-Abt F, Bentires-Alj M. How pregnancy at early age protects against breast cancer. Trends Mol Med. 2013 Dec 16. [Epub ahead of print]

Meier-Abt F, Roloff T, Brinkhaus H, Milani E, Duss S, Klebba I, Balwierz P, van Nimwegen E, Bentires-Alj M (2013) Parity induces differentiation and reduces proliferation potential and Wnt/Notch signaling ratio in mouse mammary stem cells. Breast Cancer Res 15: R36 (Highly accessed and editorial by D. Medina, BCR 2013)

Britschgi A*, Bill A*, Brinkhaus H, Rothwell C, Clay I, Duss S, Rebhan M, Raman P, Guy C, Wetzel K, George E, Oana Popa M, Lilley S, Choudhury H, Gosling M, Wang L, Fitzgerald S, Borawski J, Baffoe J, Labow M, Gaither LA**, Bentires-Alj M** (2013) The calcium activated chloride channel ANO1 promotes breast cancer progression by activating EGFR- and CAMK-signaling. PNAS plus 110:1026-34 *, ** equal contribution (Research Highlights, Nature Reviews Cancer 2013)

Britschgi A, Andraos R, Brinkhaus H, Klebba I, Romanet V, Müller U, Murakami M, Radimerski T, Bentires-Alj M (2012) JAK2/STAT5 inhibition circumvents resistance to PI3K/mTOR blockade, providing a rationale for co-targeting these pathways in metastatic breast cancer. Cancer Cell 22:796-811 (Featured by R. Abraham in Cancer Cell and by G. Wulf in BCR 2013, highlighted in Cancer Discovery 2012)

Aceto N, Duss S, Macdonald G, Meyer DS, Roloff TC, Hynes NE, Bentires-Alj M (2012) Co-expression of HER2 and HER3 receptor tyrosine kinases enhances invasion of breast cells via stimulation of interleukin-8 autocrine secretion. Breast Cancer Res. 14:R131 (Highly Accessed)

Aceto N, Sausgruber N, Brinkhaus H, Gaidatzis D, Martiny-Baron G, Mazzarol G, Confalonieri S, Quarto M, Hu G, Balwierz PJ, Pachkov M, Elledge SJ, van Nimwegen E, Stadler MB, Bentires-Alj M (2012) Tyrosine phosphatase SHP2 promotes breast cancer progression and maintains tumor-initiating cells via activation of key transcription factors and a positive feedback signaling loop. Nat Med 18: 529-37 (Featured by R. Daly in BCR)

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