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

Microscopy image, mostly blue on black background
RhoA (RhoA-GTP) activity detected using a FRET biosensor in an HT1080 cell in 3D by lattice light sheet microscopy. This image was obtained by Jianjiang Hu at our 2018 visit to the Advanced imaging center at the HHMI, Janelia research campus. Red color demarcates the highest RhoA-GTP levels observed along membrane ruffles sticking up at the front edge of the cell. Image: Jianjiang Hu

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.

Confocal image of cell in red, green and yellow
Reticular adhesions attach cells during mitotic round-up. Confocal image of a U2OS cell rounded up to undergo mitosis. The cell body is labelled by a membrane dye in red, while integrin β5 in green marks the position of reticular adhesions. From Lock et al. Nat Cell Biol 2018. Image by John Lock

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.

Illustration of cells and PAK4 in blue and purple
A new signalling pathway controlling the senescence barrier in breast cancer. Figure from Costa & Strömblad, Mol Cell Oncol 2020. Illustration by Tania Costa

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.

Group members

Staffan Strömblad

Group leader and Professor

Xiaowei Gong

Senior researcher

Helene Olofsson

Biomedical scientist

Feifei Yan

PhD student

Members of the LCI Facility

Sylvie Le Guyader

Facility Manager

Gabriela Imreh

Microscopy Engineer

Tobias Nyberg

Microscopy Engineer

Looking for a MSc, postdoc or PhD position?

Post-docs

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).

Ph.D. students

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.

Internships

We are unfortunately not able to host internships.

Selected Publications

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

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