Cell Adhesion and Cancer

Group leader

Johanna Ivaska
Academy of Finland Professor
johanna.ivaska [at] utu.fi
www.ivaskalab.com

Contact information

Turku Centre for Biotechnology
Tykistökatu 6
Turku
FI-20520
Finland

Background

Cancer cell metastasis is a leading cause of patient death worldwide. The metastatic cascade is a complex, multi-step process, beginning with the accumulation of genetic and epigenetic alterations in the primary tumour that promote local invasion, support cell proliferation and survival and promote subsequent cell dissemination to distant sites. All of these processes are critically regulated by communication between cancer cells and their non-cellular surroundings (i.e. the extracellular matrix).

Our laboratory aims to identify mechanisms that underpin cancer cell migration and invasion using different in vitro and in vivo models, high throughput screening strategies and super-resolution microscopy. In particular, we focus on the role of integrins, the major receptors for the extracellular matrix and vital players during development and tissue homeostasis, during disease progression. Importantly, abnormal regulation of integrin function has been implicated in almost every step of the metastatic cascade.

Current projects in the lab include: identification of new regulators, as well as a deeper understanding of known pathways regulating integrin activity in development and in cancer; gaining insight into receptor trafficking including pathways controlling integrin and growth factor receptor endocytosis and recycling in cancer cell invasion; determining the role of integrin signalling, in particular mechanotransduction, in supporting disease.

Research Funding

Our projects receive funding from the European Union’s Seventh Framework Programme for research, technological development and demonstration under grant agreement no. 615258 and from the Academy of Finland, the Cancer Society of Finland, the Sigrid Juselius Foundation and EMBO.
We are also part of the Translational Cancer Biology Centre of Excellence in Finland.

   

Projects

  • ERC projects
  • Regulation of integrin traffic
  • Regulation of integrin activity
  • Integrin signalling and mechanotransduction
  • Stem cell adhesions and cytoskeleton
  • Myosin X in cancer cell migration and invasion

Group Members

Technical Personnel Post-doctoral Fellows Graduate Students Research Support
Petra Laasola Maria Georgiadou Martina Lerche Hellyeh Hamidi
Jenni Siivonen Guillaume Jacquemet Johanna Lilja
Markku Saari Camilo Guzman Aki Stubb
Emilia Peuhu Pranshu Sahgal
Mika Pietilä Aleksi Isomursu
Elisa Närvä Mitro Miihkinen
Ilkka Paatero Maria Taskinen
Paulina Moreno Layseca
From left to right, 1st row: Aki Stubb, Martina Lerche and Jenni Siivonen; 2nd row: Aleksi Isomursu, Elisa Närvä, Johanna Lilja, Emilia Peuhu, Mitro Miihkinen; 3rd row: Markku Saari, Maria Rafaeva, Petra Laasola, Johanna Ivaska (The Boss); 4th row: Maria Georgiadou, Ilkka Paatero; 5th row: Tatu Aalto, Mika Pietilä, Camilo Guzman; Last row: Johanna Jukkala, Hellyeh Hamidi, Jonna Alanko, Guillaume Jacquemet

Selected Publications

Lilja J, Zacharchenko T, Georgiadou M, Jacquemet G, De Franceschi N, Peuhu E, Hamidi H, Pouwels J, Martens V, Nia FH, Beifuss M, Boeckers T, Kreienkamp H-J, Barsukov I, Ivaska J (2017) SHANK proteins limit integrin activation by directly interacting with Rap1 and R-Ras. Nat Cell Biol 19(4):292-305

Georgiadou M, Lilja J, Jacquemet G, Guzmán C, Rafaeva M, Alibert C, Yan Y, Sahgal P, Lerche M, Manneville J-B, Mäkelä T, Ivaska J (2017) AMPK negatively regulates tensin-mediated integrin activity. J Cell Biol 216(4):1107-1121

Jacquemet G, Baghirov H, Georgiadou M, Sihto H, Peuhu E, Cettour-Janet P, He T, Perälä M, Kronqvist P, Joensuu H, Ivaska J (2016) L-type calcium channels regulate filopodia stability and cancer cell invasion downstream of integrin signalling. Nat Commun 7:13297

De Franceschi N, Arjonen A, Elkhatib N, Denessiouk K, Wrobel AG, Wilson TA, Pouwels J, Montagnac G, Owen DJ, Ivaska J (2016) Selective integrin endocytosis is driven by interactions between the integrin α-chain and AP2. Nat Struct Mol Biol 23(2):172-9

Alanko J, Mai A, Jacquemet G, Schauer K, Kaukonen R, Saari M, Goud B, Ivaska J (2015) Integrin endosomal signalling suppresses anoikis. Nat Cell Biol 17(11):1412-21

Arjonen A, Kaukonen R, Mattila E, Rouhi P, Högnäs G, Sihto H, Miller BW, Morton JP, Bucher E, Taimen P, Virtakoivu R, Cao Y, Sansom OJ, Joensuu H, Ivaska J (2014) Mutant p53-associated myosin-X upregulation promotes breast cancer invasion and metastasis. J Clin Invest 24(3):1069–1082

Pouwels J, De Franceschi N. Rantakari P, Auvinen K, Karikoski M, Mattila E, Potter C, Sundberg J, Hogg N, Gahmberg CG, Salmi M, Ivaska J (2013) SHARPIN regulates uropod detachment in migrating lymphocytes. Cell Rep 5:619-28

Högnäs G, Tuomi S, Mattil E, Laine JO, Vilkki V, Murumägi A, Edgren H, Kallioniemi O and Ivaska J (2013) Aneuploidy facilitates oncogenic transformation via specific genetic alterations, including Twist2 upregulation. Carcinogenesis 9:2000-2009

Högnäs G, Tuomi S, Veltel S, Mattila E, Murumägi A, Edgren H, Kallioniemi O and Ivaska J (2012) Cytokinesis failure due to derailed integrin traffic induces aneuploidy and oncogenic transformation in vitro and in vivo. Oncogene 31:3597-3606

Pellinen T, Rantala JK, Arjonen A, Mpindi JP, Kallioniemi O and Ivaska J (2012) A functional genetic screen reveals new regulators of β1-integrin activity. J Cell Sci 125:649-661

Rantala JK, Pouwels J, Pellinen T, Veltel S, Laasola P, Mattila E, Potter C, Duffy T, Sundberg JP, Askari JA, Humphries M, Kallioniemi O, Parsons M, Salmi M and Ivaska J (2011) Sharpin is an endogenous inhibitor of β1-integrin activation. Nat Cell Biol 13(11):1315-24

Mai A, Veltel S, Pellinen T, Padzik A, Coffey E, Marjomäki V and Ivaska J (2011) Competitive binding of Rab21 and p120RasGAP to integrins regulates receptor trafficking in migrating cancer cells. J Cell Biol 194:291-306

Vuoriluoto K, Haugen H, Kiviluoto S, Mpindi JP, Nevo J, Gjerdrum C, Lorens JB and Ivaska J (2011) Vimentin regulates EMT induction and migration by governing Axl expression in breast cancer. Oncogene 30(12):1436-1448

Nevo J, Mai A, Tuomi S, Pellinen T, Pentikäinen OT, Heikkilä P, Lundin J, Joensuu H, Bono Pand Ivaska J (2010) Mammary derived growth inhibitor (MDGI) interacts with integrin α-subunits and suppresses integrin activity and invasion. Oncogene 29:6452-63

Tuomi S, Mai A, Nevo J, Laine JO, Vilkki V, Öhman TJ, Gahmberg CG,  Parker PJ and Ivaska J (2009) PKCε Regulation of an a5 Integrin–ZO-1 Complex Controls Lamellae Formation in Migrating Cancer Cells. Science Signaling, 2(77): ra32

Pellinen T, Tuomi S, Arjonen A, Wolf M, Edgren H, Meyer H, Grosse R, Kitzing T, Rantala JK, Kallioniemi O, Fässler R, Kallio, M and Ivaska J (2008) Integrin traffic regulated by Rab21 is necessary for cytokinesis. Dev Cell 15:371-385

Pellinen T, Arjonen A, Vuoriluoto K, Kallio K, Fransen JA, Ivaska J (2006) Small GTPase Rab21 regulates cell adhesion and controls endosomal traffic of beta1-integrins. J Cell Biol 173:767-80 

Mattila E, Pellinen T, Nevo J, Vuoriluoto K, Arjonen A and Ivaska J (2005) Negative regulation of EGFR signalling through integrin-alpha1beta1-mediated activation of protein tyrosine phosphatase TCPTP. Nat Cell Biol 7:78-85