Kaisa Lehti Group

Phenotypic plasticity and interchangeable modes of cell invasion and growth contribute to cancer metastasis and drug resistance, representing a major challenge in cancer research. Multiple tumor-microenvironment communication pathways are known, but it remains unclear how tumor cells integrate changes in cell-cell interactions and cues or physical confines of extracellular matrix with cytoskeletal dynamics and intracellular signaling to produce microenvironment-dependent plasticity in invasion and growth control. To date, my group has identified unique protease-receptor tyrosine kinase(RTK)-adhesion molecule interactions in tumor and stromal cells. The hypothesis from there is that these complexes form a dynamic regulatory pathway between tumor cell and its evolving microenvironment to provide plasticity in carcinoma cell functions. We also have insight on differences in such pathways in melanoma.

The objective of our future research is to define how genetic alterations, epigenetic changes, and transcriptional programs regulate the tumor cell-microenvironment communication to promote the invasion, metastasis and drug resistance of breast & ovarian cancers and melanoma. Our recent data revealed novel proteolytic regulatory mechanisms of a) lymphatic invasion, collagen assembly, and cell aggregation associated with poor melanoma prognosis (Tatti et al 2015), and b) coordination of collagen degradation, migration signaling and cytoskeletal dynamics in collective invasion or epithelial-to-mesenchymal transition-induced invasion and metastasis (Gucciardo et al 2014; von Nandelstadh et al 2014). Next we will utilize this knowledge and our gained expertise in ex vivo tissue and cellular 3D models to uncover significant (epi)genetic mechanisms behind breast & ovarian carcinoma and melanoma progression. These cancer types provide an ideal opportunity to unravel the specific impact of microenvironment on cancer progression, since they originate and spread initially in very different local microenvironments, but share a common route for dissemination via lymphatic system.


Lymphatic endothelium stimulates melanoma metastasis and invasion via MMP14-dependent Notch3 and β1-integrin activation.
Pekkonen P, Alve S, Balistreri G, Gramolelli S, Tatti-Bugaeva O, Paatero I, et al
Elife 2018 May;7():

The microenvironment of proliferative diabetic retinopathy supports lymphatic neovascularization.
Gucciardo E, Loukovaara S, Korhonen A, Repo P, Martins B, Vihinen H, et al
J. Pathol. 2018 Jun;245(2):172-185

Gremlin-1 is a key regulator of the invasive cell phenotype in mesothelioma.
Yin M, Tissari M, Tamminen J, Ylivinkka I, Rönty M, von Nandelstadh P, et al
Oncotarget 2017 Nov;8(58):98280-98297

Membrane-type matrix metalloproteases as diverse effectors of cancer progression.
Turunen S, Tatti-Bugaeva O, Lehti K
Biochim. Biophys. Acta 2017 11;1864(11 Pt A):1974-1988

RhoA knockout fibroblasts lose tumor-inhibitory capacity in vitro and promote tumor growth in vivo.
Alkasalias T, Alexeyenko A, Hennig K, Danielsson F, Lebbink R, Fielden M, et al
Proc. Natl. Acad. Sci. U.S.A. 2017 02;114(8):E1413-E1421


Liprin-α1 is a regulator of vimentin intermediate filament network in the cancer cell adhesion machinery.
Pehkonen H, von Nandelstadh P, Karhemo P, Lepikhova T, Grenman R, Lehti K, et al
Sci Rep 2016 Apr;6():24486

Proactive for invasion: Reuse of matrix metalloproteinase for structural memory.
Gucciardo E, Mobashir M, Lehti K
J. Cell Biol. 2016 Apr;213(1):11-3

Quantitative Proteomics Analysis of Vitreous Humor from Diabetic Retinopathy Patients.
Loukovaara S, Nurkkala H, Tamene F, Gucciardo E, Liu X, Repo P, et al
J. Proteome Res. 2015 Dec;14(12):5131-43

Indications of lymphatic endothelial differentiation and endothelial progenitor cell activation in the pathology of proliferative diabetic retinopathy.
Loukovaara S, Gucciardo E, Repo P, Vihinen H, Lohi J, Jokitalo E, et al
Acta Ophthalmol 2015 Sep;93(6):512-23

MMP16 Mediates a Proteolytic Switch to Promote Cell-Cell Adhesion, Collagen Alignment, and Lymphatic Invasion in Melanoma.
Tatti O, Gucciardo E, Pekkonen P, Holopainen T, Louhimo R, Repo P, et al
Cancer Res. 2015 May;75(10):2083-94

Identification of 33 candidate oncogenes by screening for base-specific mutations.
Tuupanen S, Hänninen U, Kondelin J, von Nandelstadh P, Cajuso T, Gylfe A, et al
Br. J. Cancer 2014 Oct;111(8):1657-62

Actin-associated protein palladin promotes tumor cell invasion by linking extracellular matrix degradation to cell cytoskeleton.
von Nandelstadh P, Gucciardo E, Lohi J, Li R, Sugiyama N, Carpen O, et al
Mol. Biol. Cell 2014 Sep;25(17):2556-70

Eph- and ephrin-dependent mechanisms in tumor and stem cell dynamics.
Gucciardo E, Sugiyama N, Lehti K
Cell. Mol. Life Sci. 2014 Oct;71(19):3685-710

EphA2 cleavage by MT1-MMP triggers single cancer cell invasion via homotypic cell repulsion.
Sugiyama N, Gucciardo E, Tatti O, Varjosalo M, Hyytiäinen M, Gstaiger M, et al
J. Cell Biol. 2013 Apr;201(3):467-84

EphA2 bears plasticity to tumor invasion.
Sugiyama N, Gucciardo E, Lehti K
Cell Cycle 2013 Sep;12(18):2927-8

MT1-MMP inactivates ADAM9 to regulate FGFR2 signaling and calvarial osteogenesis.
Chan K, Wong H, Jin G, Liu B, Cao R, Cao Y, et al
Dev. Cell 2012 Jun;22(6):1176-90

KSHV-initiated notch activation leads to membrane-type-1 matrix metalloproteinase-dependent lymphatic endothelial-to-mesenchymal transition.
Cheng F, Pekkonen P, Laurinavicius S, Sugiyama N, Henderson S, Günther T, et al
Cell Host Microbe 2011 Dec;10(6):577-90

Membrane-type-3 matrix metalloproteinase (MT3-MMP) functions as a matrix composition-dependent effector of melanoma cell invasion.
Tatti O, Arjama M, Ranki A, Weiss S, Keski-Oja J, Lehti K
PLoS ONE 2011 ;6(12):e28325

Notch restricts lymphatic vessel sprouting induced by vascular endothelial growth factor.
Zheng W, Tammela T, Yamamoto M, Anisimov A, Holopainen T, Kaijalainen S, et al
Blood 2011 Jul;118(4):1154-62

Syndecan-1 and -4 differentially regulate oncogenic K-ras dependent cell invasion into collagen through α2β1 integrin and MT1-MMP.
Vuoriluoto K, Högnäs G, Meller P, Lehti K, Ivaska J
Matrix Biol. 2011 Apr;30(3):207-17

FGF receptor-4 (FGFR4) polymorphism acts as an activity switch of a membrane type 1 matrix metalloproteinase-FGFR4 complex.
Sugiyama N, Varjosalo M, Meller P, Lohi J, Chan K, Zhou Z, et al
Proc. Natl. Acad. Sci. U.S.A. 2010 Sep;107(36):15786-91

Fibroblast growth factor receptor 4 regulates tumor invasion by coupling fibroblast growth factor signaling to extracellular matrix degradation.
Sugiyama N, Varjosalo M, Meller P, Lohi J, Hyytiäinen M, Kilpinen S, et al
Cancer Res. 2010 Oct;70(20):7851-61

Group Members

Senior researcher

Kaisa Lehti

Phone: +46-(0)8-524 852 54
Organizational unit: Kaisa Lehti group
E-mail: kaisa.lehti@ki.se


Pauliina Turunen

Phone: +46-(0)(0)73-625 14 75
Organizational unit: Kaisa Lehti group
E-mail: pauliina.turunen@ki.se

Research assistant

Mina Eriksson

Organizational unit: Kaisa Lehti group
E-mail: mina.eriksson@ki.se

Graduate Student

Lidia Moyano Galceran

Organizational unit: Department of Microbiology, Tumor and Cell Biology (MTC), C1
E-mail: lidia.moyano.galceran@ki.se


Yuichiro Miki

Organizational unit: Kaisa Lehti group
E-mail: yuichiro.miki@ki.se

Twana Hasseb Abdulahad AlkasaliasAssociated
Mina ErikssonResearch assistant
Kaisa LehtiSenior researcher
Yuichiro MikiAssociated, Postdoc
Lidia Moyano GalceranPhD student, Graduate Student
Pauliina TurunenPostdoc