The Signaling Group – University of Copenhagen

The Signaling Group

Lysosomes, Invasion and Signaling group (L-INS): Lysosomes as therapeutic targets in invasive and metastatic cancers.

Background

Metastasis is responsible for about 90% of cancer deaths, thus novel and innovative strategies are needed for its effective targeting. Our current work is focused in the role of lysosomes in the invasiveness of the aggressive, therapy resistant breast cancers. Lysosomes are important intracellular degradation units that cells also use for other specific functions such as lysosomal secretion, also known as lysosomal exocytosis. Lysosomal exocytosis is an important process that is needed for the daily maintenance of cellular homeostasis. Cancer cells are able to amplify and “hijack” this “housekeeping” lysosomal secretion and use it to modify the extracellular microenvironment to favor invasion and metastasis. Understanding of how this works can facilitate the development of treatments against aggressive cancer forms.

Main research areas

We are currently focusing our research on the role and function of Myeloid Zinc Finger 1 (MZF1) and lysosome distribution in breast cancer invasion and metastasis. We are also screening for new inhibitors for HER2-induced invasive breast cancer using libraries of drugs that are approved for use in humans.

Research methods

 Gene expression and activity analysis (reporter assays, chromatin immunoprecipitation and quantitative PCR); microRNA studies (expression, analysis, inhibition etc.); RNA interference studies (siRNA, shRNA); Signal transduction studies (phosphorylation, dephosphorylation and SUMOylation); Lentivirus and retrovirus production, infection, analysis; CRISPR/Cas9 knockout technology; High throughput drug and siRNA screening with different readouts e.g. fluorescent redistribution and enzymatic activity; Growth and invasion of breast cancer cell spheroids in 3D cultures; Isolation, growth and analysis of mammary cancer organoids; Mouse xenograft studies (mammary cancer).

Funding

KBVU; DFF-FSS; the Danish Agency for Science, Technology and Innovation, Novonordisk Fonden.