Molecular cancer and stem cell therapeutics
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.
Image: Evidence of EMT in invasive human invasive breast cancer. Loss of tight junctional proteins (CAR protein, lilac) is associated with nuclear co-expression of Smad4 (green) and Snail (red) and invasion into the stroma (black). Cell Cycle 2010 Jun;9(12):2363-74
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.
|Theresa Vincent||Research group leader|
|Jennifer Feenstra||Post doc|
|Varsha Prakash||PhD student|
|Theresa Mader||Research and development intern|
Group members outside Karolinska Institutet
|Linda Bojmar||PhD student (shared with Dr Lyden, Weill Cornell Medical College of Cornell University)|
|Randall Dass||PhD student (shared with Dr Blanchard, Weill Cornell Medical College of Cornell University)|
- Jacob Jansson
- Iris Muller
- Tianyi Song
- Rithika Venkatesh
- Joel Östblom
Theresa Vincent's research presentation at the Department of Physiology and Biophysics, Cornell University, Weill Cornell Medical College, New York, USA.
- Swedish Research Council
- Karolinska Institutet
- Swedish Cancer Society
- Tore Nilsson Foundation (site in Swedish)
- Magnus Bergvall Foundation (site in Swedish)
- Mary Beves Brain Childhood foundation
- Vinnova-Vinnmer Marie-Curie International Qualification
- Sigurd and Elsa Golje's grant
- Starr Foundation
- DoD BCRP Breast cancer Breakthrough Award
- Åke Wiberg Foundation (site in Swedish)
How a particular gene protects against aggressive breast cancer. News article from KI. 2016.08.08
Face morphogenesis is promoted by Pbx-dependent EMT via regulation of during frontonasal prominence fusion.
Development 2018 03;145(5):
Variant ribosomal RNA alleles are conserved and exhibit tissue-specific expression.
Sci Adv 2018 Feb;4(2):eaao0665
EMT, inflammation and metastasis.
Semin. Cancer Biol. 2017 12;47():168-169
Membrane depolarizing channel blockers induce selective glioma cell death via impaired nutrient transport and unfolded protein / amino acid responses.
Niklasson M, Maddalo G, Zuzana Sramkova Z, Mutlu E, Wee S, Sekyrova S, Schmidt L, Fritz N, Ivar Dehnisch I, Kyriatzis G, Krafcikova M, Carson BBC, Feenstra J, Marinescu V, Segerman A, Mulder J, Haraldsson M, Gustavsson AL, Hammarström L, Jenmalm, Jensen A, Uhrbom L, Altelaar A.F. M, Linnarsson S, Uhlén P, Trantirek L, Vincent CT, Nelander S, Per Øyvind Enger PO, Andäng M.
Cancer Res. (2017) Jan 13
Wnt5a Signals through DVL1 to Repress Ribosomal DNA Transcription by RNA Polymerase I.
PLoS Genet. 2016 Aug;12(8):e1006217
Functional Dynamics within the Human Ribosome Regulate the Rate of Active Protein Synthesis
Ferguson A, Wang L, Altman R, Terry D, Juette M, Burnett B, et al
Molecular Cell. (2015) 60:1–12
Dysregulation of PAD4-mediated citrullination of nuclear GSK3β activates TGF-β signaling and induces epithelial-to-mesenchymal transition in breast cancer cells.
Proc. Natl. Acad. Sci. U.S.A. 2013 Jul;110(29):11851-6
A SNAIL1-SMAD3/4 transcriptional repressor complex promotes TGF-beta mediated epithelial-mesenchymal transition.
Nat. Cell Biol. 2009 Aug;11(8):943-50
The glycogen synthase kinase (GSK) 3beta represses RNA polymerase I transcription.
Oncogene 2008 Sep;27(39):5254-9
Neutralized adenovirus-immune complexes can mediate effective gene transfer via an Fc receptor-dependent infection pathway.
J. Virol. 2006 Oct;80(20):10237-47
Cytokine-mediated downregulation of coxsackievirus-adenovirus receptor in endothelial cells.
Vincent T, Pettersson RF, Crystal RG, Leopold PL.
J Virol. (2004) 78:8047-58.
Rapid assessment of adenovirus serum neutralizing antibody titer based on quantitative, morphometric evaluation of capsid binding and intracellular trafficking: population analysis of adenovirus capsid association with cells is predictive of adenovirus infectivity.
J. Virol. 2001 Feb;75(3):1516-21
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
In memory of Professor Ralf Pettersson (1945-2011) and Professor Lennart Philipson (1929-2011).
Semin. Cancer Biol. 2012 Oct;22(5-6):359-488
A dialogue with Dr. Craig B. Thompson about metabolism and its relevance for tumor growth, progression and metastasis.
Semin. Cancer Biol. 2012 Oct;22(5-6):484-8
A new paradigm for mechanobiological mechanisms in tumor metastasis.
Semin. Cancer Biol. 2012 Oct;22(5-6):385-95
Transcriptional crosstalk between TGF-β and stem cell pathways in tumor cell invasion: role of EMT promoting Smad complexes.
Cell Cycle 2010 Jun;9(12):2363-74
Published commentaries on our research work
News and Views on our published article Transcriptional crosstalk between TGF-β and stem cell pathways in tumor cell invasion: role of EMT promoting Smad complexes.
Cell Cycle (2010) 12: 2363-2374
Integration of transcriptional signals at the tumor cell invasive front.
Cell Cycle 2010 Jul;9(13):2499-500
A spotlight on regulatory networks connecting EMT and cancer stem cells.
Cell Cycle 2010 Aug;9(15):2927