Cell Biology of Cancer - Staffan Strömblad
Our research focuses on key cellular events in cancer progression, with emphasis on cell migration and p21-activated kinase 4 (Pak4).
Depending on the properties of the surrounding extracellular matrix, cancer cells can utilize different migration strategies for dissemination. This adaptive behavior expands the range of tissue contexts under which cancer cells can efficiently invade. Expanding on this knowledge, we recently identified two distinct modes of mesenchymal migration and that perturbing cell-ECM interactions or tensile forces caused switching between these modes. We combine different quantitative microscopy techniques, including traction force microscopy and FRET signaling biosensors aiming to reveal mechanisms of migration mode switching and how distinct temporal phases are controlled and executed. These studies are expected to provide novel treatment opportunities targeting the most malignant aspect of any cancer, the ability to metastasize.
Pak4 is overexpressed in several human cancers and we previously linked Pak4 to promotion of cancer cell migration and to control of cell growth. To examine the role of Pak4 in cancer progression, our laboratory has in place a number of techniques, including in vitro models, transgenic mice, cancer mouse models, patient database bioinformatics and patient derived material, which are combined within our comprehensive yet molecularly detailed investigations, stretching also into testing Pak4 pharmacological targeting.
We have a large number of national and international collaborations and actively participate in different networks, including the European Union-H2020-Multimot project, the Swedish pan-university project “Systems microscopy of cancer cell migration” and the Karolinska Institute’s Breast Cancer Theme Center (BRECT) of which Strömblad is the vice director. Strömblad is also director of the Live Cell Imaging facility located at the Department of Biosciences and Nutrition of Karolinska Institutet.
We are also participating in a research program entitled Use of Systems Microscopy to Understand Cancer Cell Migration.
Reticular adhesions are a distinct class of cell-matrix adhesions that mediate attachment during mitosis.
Nat. Cell Biol. 2018 11;20(11):1290-1302
KIF13A-regulated RhoB plasma membrane localization governs membrane blebbing and blebby amoeboid cell migration.
EMBO J. 2018 Sep;37(17):
Active and inactive β1 integrins segregate into distinct nanoclusters in focal adhesions.
J. Cell Biol. 2018 06;217(6):1929-1940
Using Systems Microscopy to Understand the Emergence of Cell Migration from Cell Organization.
Methods Mol. Biol. 2018 ;1749():119-134
Inflammation-Sensitive Myosin-X Functionally Supports Leukocyte Extravasation by Cdc42-Mediated ICAM-1-Rich Endothelial Filopodia Formation.
J. Immunol. 2018 03;200(5):1790-1801
Identification of the PAK4 interactome reveals PAK4 phosphorylation of N-WASP and promotion of Arp2/3-dependent actin polymerization.
Oncotarget 2017 Sep;8(44):77061-77074
Pdx1-Cre-driven conditional gene depletion suggests PAK4 as dispensable for mouse pancreas development.
Sci Rep 2017 08;7(1):7031
An analysis toolbox to explore mesenchymal migration heterogeneity reveals adaptive switching between distinct modes.
Elife 2016 Jan;5():e11384
p21-activated kinase group II small compound inhibitor GNE-2861 perturbs estrogen receptor alpha signaling and restores tamoxifen-sensitivity in breast cancer cells.
Oncotarget 2015 Dec;6(41):43853-68
Disentangling Membrane Dynamics and Cell Migration; Differential Influences of F-actin and Cell-Matrix Adhesions.
PLoS ONE 2015 ;10(8):e0135204
Non-monotonic cellular responses to heterogeneity in talin protein expression-level.
Integr Biol (Camb) 2015 Oct;7(10):1171-85
RING finger protein 31 promotes p53 degradation in breast cancer cells.
Oncogene 2016 Apr;35(15):1955-64
A plastic relationship between vinculin-mediated tension and adhesion complex area defines adhesion size and lifetime.
Nat Commun 2015 Jun;6():7524
Plasticity in the macromolecular-scale causal networks of cell migration.
PLoS ONE 2014 ;9(2):e90593
Focal adhesion disassembly is regulated by a RIAM to MEK-1 pathway.
J. Cell. Sci. 2012 Nov;125(Pt 22):5338-52
Protein kinase Cα (PKCα) regulates p53 localization and melanoma cell survival downstream of integrin αv in three-dimensional collagen and in vivo.
J. Biol. Chem. 2012 Aug;287(35):29336-47
PRIMA-1Met/APR-246 induces wild-type p53-dependent suppression of malignant melanoma tumor growth in 3D culture and in vivo.
Cell Cycle 2011 Jan;10(2):301-7
Rap1-GTP-interacting adaptor molecule (RIAM) protein controls invasion and growth of melanoma cells.
J. Biol. Chem. 2011 May;286(21):18492-504
p21-activated kinase 4 regulates ovarian cancer cell proliferation, migration, and invasion and contributes to poor prognosis in patients.
Proc. Natl. Acad. Sci. U.S.A. 2010 Oct;107(43):18622-7
Integrin-mediated cell attachment induces a PAK4-dependent feedback loop regulating cell adhesion through modified integrin alpha v beta 5 clustering and turnover.
Mol. Biol. Cell 2010 Oct;21(19):3317-29
PtdIns(3,4,5)P₃ is a regulator of myosin-X localization and filopodia formation.
J. Cell. Sci. 2010 Oct;123(Pt 20):3525-34
p21-activated kinase 4 phosphorylation of integrin beta5 Ser-759 and Ser-762 regulates cell migration.
J. Biol. Chem. 2010 Jul;285(31):23699-710
Available postdoc positions are generally announced at Karolinska Institutet’s KI-jobs page. However, outstanding candidates are welcome to apply at any time; Please send an introductory letter, CV, publication list, and three letters of reference to Staffan.Stromblad@ki.se. (Considered to be outstanding candidates are those who would be competitive for prestigious external fellowships, such as the EMBO long term fellowships).
All Ph.D. student positions will be announced at KI-jobs web page when available.
Master’s thesis students
For Master’s student projects (minimal time one term), please inquire with Staffan Strömblad. Please provide, in addition to information on timing, formal requirements, etc., also a cover letter of intent, CV, a copy of your University grades and at least two letters of reference.
We are unfortunately not able to host internships.
The Strömblad laboratory is currently supported by grants from:
-The Swedish Foundation for Strategic Research.
-The Swedish Research Council.
-The Swedish Cancer Society.
-The Swedish Childhood Cancer Foundation.
Dept. of Biosciences and Nutrition
Huddinge (Flemingsberg), Sweden
Department of Biosciences and Nutrition, Neo
SE-141 83 Huddinge Sweden