Cancer Invasion and Resistance

The aim of our research is to understand cancer-induced molecular changes, especially those that regulate lysosomal activity and function leading to enhanced invasion and metastasis, in order to find novel ways to target these often still untreatable, malignant functions of cancer.

Our current work is focused on the role and function of HER2 signaling and lysosomes in aggressive and therapy resistant breast cancer and on identifying novel, personalized treatment strategies against platinum-taxane resistant ovarian cancer by targeting lysosomes. In our research, we use 3D cell cultures, breast and ovarian cancer organoids, and various cell and molecular biology approaches including high throughput microscopy and CRISPR-Cas9 technology. 

Selected publications:

Skorda A, Lauridsen AR, Wu C, Huang J, Mrackova M, Jank V, Sztupinski Z, Strauss R, Bilgin M, Maeda K, Liu B, Luo Y, Jäättelä M, Kallunki T: Activation of invasion by oncogenic reprogramming of cholesterol metabolism via increased NPC1 expression and macropinocytosis. Oncogene 2023; 42:2495–2506

Lahtinen A, Lavikka K, Virtanen A, Li Y, Jamalzadeh S, Skorda A, Lauridsen AR, Zhang K, Marchi G, Isoviita VM, Ariotta V, Lehtonen O, Muranen TA, Huhtinen K, Carpén O, Hietanen S, Senkowski W, Kallunki T, Häkkinen A, Hynninen J, Oikkonen J, Hautaniemi S: Evolutionary states and trajectories characterized by distinct pathways stratify ovarian high-grade serous carcinoma patients. Cancer Cell 2023;41(6):1103-1117

Skorda A, Bay ML, Hautaniemi S, Lahtinen A, Kallunki T: Kinase inhibitors in the treatment ofovarian cancer: current state and future promises. Cancers 2022: 14(24):6257

Hansen MB, Postol M, Tvingsholm S, Nielsen IØ, Dietrich TN, Puustinen P, Maeda K, Dinant C, Strauss R, Egan D, Jäättelä M, Kallunki T:  Identification of lysosome-targeting drugs with anti-inflammatory activity as potential invasion inhibitors of treatment resistant HER2 positive cancers. Cell Oncol 2021: 44(4):805-820

Brix DM, Tvingsholm SA, Hansen MB, Clemmensen KB, Ohman T, Siino V, Lambrughi M, Hansen K, Puustinen P, Gromova I, James P, Papaleo E, Varjosalo M, Moreira J, Jäättelä M, Kallunki T: Release of transcriptional repression via ErbB2-induced, SUMO-directed phosphorylation of Myeloid Zinc Finger-1 Serine 27 activates lysosome redistribution and invasion. Oncogene 2021: 38(17):3170-3184