Cell Biology of Cancer - Staffan Strömblad
All tissue cells are surrounded by an extracellular matrix (ECM). Cell-matrix interactions control cell proliferation, survival, migration and differentiation, all key processes in cancer development and progression. We study the nature of cell-matrix interactions and how these interactions influence key cellular functions, including cell proliferation and migration.
Cell-Matrix Interactions and Signalling in Cancer
Part of the ECM influence on cancer cells stems from the mechanical properties of the ECM. Stiffening of a tumour as a palpable lump is also often the first diagnostic measure of cancer; normal breast is soft, whereas breast cancer is stiffer. Increased stiffness is a physical hallmark of many solid cancers, including breast cancer, where the increased extracellular matrix stiffness contributes to oncogenic transformation, aggressiveness and poor prognosis.
We study, at the molecular level, how the mechanical properties of the ECM generate intracellular signalling in cancer cells and how these signals promote cell proliferation and migration.
Also, cancer cells attach to and can migrate within the ECM, ultimately leading to life-threatening metastasis. We study cancer cell migration with the purpose to uncover new molecular mechanisms governing this process. We are particularly interested in how local force generation and signaling of small GTPases of the Rho family coordinate their actions to produce cell migration. For this purpose, we use quantitative live cell imaging combined with advanced image analysis and modelling.
We also investigate how the signalling component p21-activated kinase-4 (PAK4) affects cancer development and progression, in particular the control of cellular senescence, a cellular stress response that serves as an early barrier to cancer development.
Our detailed molecular studies of cancer development and progression are aimed to aid the development of urgently needed new diagnosis and therapy.
News from the group
Members of the LCI Facility
Looking for a MSc, postdoc or PhD position?
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.
New control of the senescence barrier in breast cancer.
Costa TDF, Strömblad S
Mol Cell Oncol 2020 ;7(2):1684129
PAK4 suppresses RELB to prevent senescence-like growth arrest in breast cancer.. Costa TDF, Zhuang T, Lorent J, Turco E, Olofsson H, Masia-Balague M, et al. Nat Commun 2019 08;10(1):3589
Normal mammary gland development after MMTV-Cre mediated conditional PAK4 gene depletion. Rabieifar P, Zhuang T, Costa TDF, Zhao M, Strömblad S. Sci Rep 2019 Oct;9(1):14436
Clathrin-containing adhesion complexes.. Lock JG, Baschieri F, Jones MC, Humphries JD, Montagnac G, Strömblad S, et al. J. Cell Biol. 2019 Jul;218(7):2086-2095
Reticular adhesions are a distinct class of cell-matrix adhesions that mediate attachment during mitosis. Lock JG, Jones MC, Askari JA, Gong X, Oddone A, Olofsson H, et al. Nat. Cell Biol. 2018 11;20(11):1290-1302
KIF13A-regulated RhoB plasma membrane localization governs membrane blebbing and blebby amoeboid cell migration. Gong X, Didan Y, Lock JG, Strömblad S. EMBO J. 2018 Sep;37(17):
Active and inactive β1 integrins segregate into distinct nanoclusters in focal adhesions. Spiess M, Hernandez-Varas P, Oddone A, Olofsson H, Blom H, Waithe D, et al. J. Cell Biol. 2018 06;217(6):1929-1940
Using Systems Microscopy to Understand the Emergence of Cell Migration from Cell Organization. Strömblad S, Lock JG. Methods Mol. Biol. 2018 ;1749():119-134
Inflammation-Sensitive Myosin-X Functionally Supports Leukocyte Extravasation by Cdc42-Mediated ICAM-1-Rich Endothelial Filopodia Formation. Kroon J, Schaefer A, van Rijssel J, Hoogenboezem M, van Alphen F, Hordijk P, et al. 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. Zhao M, Spiess M, Johansson HJ, Olofsson H, Hu J, Lehtiö J, et al. Oncotarget 2017 Sep;8(44):77061-77074
Pdx1-Cre-driven conditional gene depletion suggests PAK4 as dispensable for mouse pancreas development. Zhao M, Rabieifar P, Costa TDF, Zhuang T, Minden A, Löhr M, et al. Sci Rep 2017 08;7(1):7031
An analysis toolbox to explore mesenchymal migration heterogeneity reveals adaptive switching between distinct modes. Shafqat-Abbasi H, Kowalewski JM, Kiss A, Gong X, Hernandez-Varas P, Berge U, et al. Elife 2016 Jan;5():e11384
RING finger protein 31 promotes p53 degradation in breast cancer cells. Zhu J, Zhao C, Zhuang T, Jonsson P, Sinha I, Williams C, et al. Oncogene 2016 Apr;35(15):1955-64
A plastic relationship between vinculin-mediated tension and adhesion complex area defines adhesion size and lifetime. Hernández-Varas P, Berge U, Lock JG, Strömblad S. Nat Commun 2015 Jun;6():7524
Plasticity in the macromolecular-scale causal networks of cell migration. Lock JG, Mamaghani MJ, Shafqat-Abbasi H, Gong X, Tyrcha J, Strömblad S. PLoS ONE 2014 ;9(2):e90593