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Cancer Progression and Metastasis

Junior Research Group Cancer Progression and Metastasis

Dr. Rene-Filip Jackstadt

Microscopy image of a liver metastasis (colorectal cancer cells in brown).
© dkfz.de

Cancer metastasis is the major cause of death in the majority of solid cancers. Therefore, our aim is to understand the mechanisms that control cancer progression and metastasis in order to identify novel implications for the clinics. Metastasis is a multistep process, with a complex evolution, where cells leave the primary tumor and seed to distant organs. Every step during metastasis adds considerable heterogeneity to the tumor and includes the acquisition of stem cell features. These cancer stem cell populations have distinct molecular, genetic and phenotypic features, which jointly increase the risk of therapy resistance. However, the tumor microenvironment can control phenotypic plasticity of cancer stem cells.

We utilize unbiased multi-omics (transcriptome, epigenome, methylome) at single cell level, functional genomics and lineage tracing approaches to analyze stem cell plasticity with complex in vivo models of metastatic colorectal cancer. These genetically engineered mouse models contain alterations and show progression similarly to human metastatic colorectal cancer. Further, these models allow tumor progression in the native tumor microenvironment, which enables us to investigate the role of non-cell-autonomous factors that control cancer stem cells features during metastasis. Our lab has a strong expertise in the use of genetically engineered mouse models, to analyze each step of molecular and cellular changes during the metastatic process longitudinally and in response to therapy. We also use primary clinical samples and patient derived organoids to better understand the most lethal stages of the disease.

To understand the mechanisms of colorectal cancer progression this division will focus on the following major topics:

  • Functional characterization of cancer stem cells in tumor-evolution
  • Molecular and cellular basis of cancer stem cell niches
  • Analysis of cancer stem cells and the interaction with the tumor microenvironment as driver of therapy resistance
Our research will broaden our understanding of the mechanisms that control colorectal cancer progression and will help to find therapeutic vulnerabilities of late stage cancers.

Contact

Dr. Rene-Filip Jackstadt
Cancer Progression and Metastasis (A013)
Deutsches Krebsforschungszentrum
Im Neuenheimer Feld 280
69120 Heidelberg
Tel: +49 6211/423928

Selected Publications

  • Jackstadt R, van Hooff SR, Leach JD, Cortes-Lavaud X, Lohuis JO, Ridgway RA, Wouters VM, Roper J, Kendall TJ, Roxburgh CS, Horgan PG, Nixon C, Nourse C, Gunzer M, Clark W, Hedley A, Yilmaz OH, Rashid M, Bailey P, Biankin AV, Campbell AD, Adams DJ, Barry ST, Steele CW, Medema JP, Sansom OJ (2019). Epithelial NOTCH signaling rewires the tumor microenvironment of colorectal cancer to drive poor-prognosis subtypes and metastasis. Cancer Cell. 16;36(3):319-336.e7
  • Schmidt S*, Gay D*, Uthe FW*, Denk S, Paauwe M, Matthes N, Diefenbacher ME, Bryson S, Warrander FC, Erhard F, Ade CP, Baluapuri A, Walz S, Jackstadt R, Ford C, Vlachogiannis G, Valeri N, Otto C, Schu?lein-Völk C, Maurus K, Schmitz W, Knight JRP, Wolf E, Strathdee D, Schulze A, Germer CT, Rosenwald A, Sansom OJ, Eilers M, Wiegering A (2019) A MYC/GCN2/eIF2a negative feedback loop limits protein synthesis to prevent MYC-dependent apoptosis in colorectal cancer. Nature Cell Biol. 21(11):1413-1424
  • Jackstadt R, Sansom OJ. (2016). Mouse models of intestinal cancer. J Pathol. 238(2):141-51
  • Jackstadt R, Röh S, Neumann J, Jung P, Hoffmann R, Horst D, Berens C, Bornkamm GW, Kirchner T, Menssen A, Hermeking H. (2013). AP4 is a mediator of epithelial-mesenchymal transition and metastasis in colorectal cancer. J Exp Med. 1;210(7):1331-50
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