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|Evidence of EMT in invasive human breast cancer. Loss of CAR-positive tight junctions (violet) is associated with nuclear co-expression of Smad4 (green) and Snail1 (red) and tumor cell invasion into the stroma (black) (image taken from Cell Cycle, 2010)|
Ninety percent of all cancer deaths arise from tumor metastasis, a process that depends on the delamination and spread of tumor cells. Only a minority of the tumor cells, i.e. tumor-initiating cells also referred to as cancer stem cells (CSCs), are capable of successfully seeding a distant site. The CSC hypothesis proposes that only a subset of tumor cells have the ability to self-renew and are thus responsible for driving tumorigenesis, making them ideal targets for cancer intervention. Our research group focuses on the early steps of the metastatic process, i.e. migration and invasion of the tumor cells into circulation through a process known as epithelial to mesenchymal transition (EMT) and the mechanisms controlling this process. Recent discoveries have provided the compelling evidence that during the process of EMT cells are converted into cancer stem cells (CSCs). The fact that cells acquire stem-like traits during the process of migration, invasion and intravasion i.e. EMT, opens up a new and exciting area of research - merging stem cell biology and cancer biology. It also highlights the need for further EMT research within the cancer field.
Our main interest is to gain a better understanding of cellular changes that induces EMT and conversion to CSCs. We are studying the role of cell signaling such as TGFb and Wnt and its role in migration and spread of cancers including breast and glioma using both in-vitro and in-vivo models. Of particular interest is the emerging area of epigenetics and metabolism and its importance for EMT. Another interest is in menchanobiology thus how mechanical pressure within the tumors micro/nanoenvironment will affect metastasis. Our long-term goal is that these studies will provide significant insight into the complex mechanism of tumor spread and metastasis and ultimately allow for our research to advance into a clinical setting.
Currently, we have several ongoing national and international research projects within these areas and our laboratory places a special focus on international collaborative efforts. It is our ambition to create a unique laboratory and educational environment that is not limited by departmental or national barriers but only by our scientific education, curiosity and ambition.
Our lab, at the Department of Medicine, is part of the research team of Cell and Molecular Immunology, which is located at the Centrum for Molecular Medicine (CMM). CMM brings together more than 400 researchers both with clinical experience from the Karolinska University Hospital but also with basic research expertise from KI.
We are currently looking for highly motivated scientists and students to join our research group. Please contact Theresa Vincent with inquiries including a letter of research interests, CV and recommendation letter.
We are very grateful to our funding agencies, which are currently supporting our research
- Swedish Research Council
- Swedish National Cancer foundation
- Tore Nilssons foundation
- Magnus Bergvall foundation
- Mary Beves Brain Childhood foundation
- Vinnova-Vinnmer Marie-Curie International Qualification
- Sigurd och Elsa Goljes Grant
Enhanced liver uptake of opsonized red blood cells after in vivo transfer of FcgammaRIIA cDNA to the liver.
Blood 1999 Nov;94(10):3448-55
Neutralized adenovirus-immune complexes can mediate effective gene transfer via an Fc receptor-dependent infection pathway.
J. Virol. 2006 Oct;80(20):10237-47
A SNAIL1-SMAD3/4 transcriptional repressor complex promotes TGF-beta mediated epithelial-mesenchymal transition.
Nat. Cell Biol. 2009 Aug;11(8):943-50
Vincent T och Fuxe J.
Ny upptäckt kan leda till terapi mot metastaser
Onkologi i Sverige (2009) 6