Tumor cell plasticity
James Lorens group.
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Epithelial cell plasticity between epithelial and mesenchymal phenotypic states provides the repertoire of cellular functions required during embryonic development, organogenesis and adult tissue repair and homeostasis. This phenotypic plasticity also allows adaptation of tumor cells to microenvironmental challenges such as hypoxia, inflammation and drug treatment that facilitate malignant progression, metastasis and drug resistance. Gene expression programs related to the epithelial-to-mesenchymal transition (EMT) are utilized both by normal and neoplastic epithelial cells to access stem cell-related functions.
Using comparative functional approaches, we are investigating the relationship between regulators EMT in tumor cells in maintenance of normal stem and progenitor cells. Our recent results highlight the Axl receptor tyrosine kinase as a key regulator of adult epithelial and carcinoma cell plasticity. Mechanistic studies on Axl signaling have provided new insights into tumor EMT regulation and formed the basis for the recent clinical translation of novel Axl inhibitors.
We are further investigating how distinct combinations of microenvironmental factors regulate phenotypic plasticity in normal and cancer cells using new a screening technology (MEArrays). Using these mechanistic insights we are exploring how microenvironmental factors regulate tumor cell plasticity underlying contextual drug responses.
Staff
Bougnaud, Sebastien - PhD
Davidsen, Kjersti - MD
Engelsen, Agnete - PhD
Ertsås, Henriette - MSc
Haaland, Gry - MD
Jokela, Tiina - PhD
Pelissier, Fanny - MSc
Tiron, Crina - MSc
Vik Berge, Sissel – senior engineer
Key publications
Labarge MA, Parvin B, Lorens JB (2014) Molecular deconstruction, detection, and computational prediction of microenvironment-modulated cellular responses to cancer therapeutics. Adv Drug Deliv Rev. in press.
Evensen L, Odlo K, Micklem DR, Littlewood-Evans A, Wood J, Kuzniewski C, Altmann KH, Hansen TV, Lorens JB. (2013) Contextual compound screening for improved therapeutic
discovery. Chembiochem 14:2512-8.
Mora-Blanco LE, Lorens, JB, LaBarge, MA. (2013) The Tumor Microenvironment as a Transient Niche: A Modulator of Epigenetic States and Stem Cell Functions. Trends in Stem Cell Proliferation and Cancer Research, p.463-78
Ben-Batalla I, Schultze A, Wroblewski M, Erdmann R, Heuser M, Waizenegger JS, Riecken K, Binder M, Schewe D, Sawall S, Witzke V, Cubas-Cordova M, Janning M, Wellbrock J, Fehse B, Hagel C, Krauter J, Ganser A, Lorens JB, Fiedler W, Carmeliet P, Pantel K, Bokemeyer C, Loges S. (2013) Axl, a prognostic and therapeutic target in acute myeloid leukemia mediatesparacrine crosstalk of leukemia cells with bone marrow stroma. Blood 122:2443-52.
Gjerdrum, C., Tiron, C.E., Micklem, D.R., Høiby, T., Steffansson, I., Haugen, H, Sandal, T., McCormack, E., Gjertsen, B.T., Akslen, L., C. Glackin and Lorens, J.B. (2010) Axl is an essential epithelial-to-mesenchymal transitioninduced regulator of breast cancer metastasis
and patient survival. Proc. Natl. Acad. Sci. USA, 107: 1124-1129