Cancer and Inflammation Laboratory

Laboratory overview

The Cancer and Inflammation Laboratory focuses on dissecting molecular mechanisms that link inflammation to tumour development, which is often facilitated through interactions between tumour cells and the highly abundant inflammatory molecules and cells within the tumour microenvironment. Although the molecular mechanisms that underpin tumour promotion may vary among different types of epithelial cancers, these mechanisms converge in tumour cells on the shared transcription factors NF-κB and Stat3. While they both promote cell survival, excessive Stat3 activity also facilitates tumour proliferation, invasion, blood-vessel growth and a metabolic switch.

By understanding how tumor cells respond to inflammatory signals we can develop treatments that target and interfere with these signals to prevent cancer growth. Prof. Matthias Ernst, Scientific Director, ONJCRI
170330 ONJCRI 0162 170330 ONJCRI 0244 laboratories2260

Our focus

Stat3 and tumourigenesis

Pronounced epithelial Stat3 activity is not only observed during wound-healing, but also readily detected in a majority of cancers including those arising in the colon, stomach, breast and lung. Our lab recently established a novel link whereby the cytokine interleukin (IL)-11, through its shared gp130 receptor, the associated Jak kinases and Stat3 signaling, promotes tumourigenesis. Surprisingly, this signaling cascade also become rate limiting for the growth of colon and gastric tumours that are driven by mutations in other well recognized cancer pathways. 

Neoplastic cells

We are also therapeutically exploiting differences in signaling threshold requirements between normal and neoplastic cells. For instance, oncogenic activation of the WNT/beta-catenin signaling cascade, which often comprises cooperating genetic and/or epigenetic events, is the most common tumour-initiating hallmark in neoplastic intestinal stem cells for sporadic colorectal cancer. Because interference with the gp130/Stat3 signaling cascades limits the expansion of such intestinal (cancer) stem cells, the Stat3-mediated non-oncogene addiction dependency can be therapeutically targeted in WNT-dependent tumourigenesis or in regenerative medicine.

Hck activation

The cellular composition of the tumour microenvironment affects how well a tumour can grow and the extent to which it responds to targeted and immune-modulatory therapy. Although these processes are affected by many different cell types within the tumour stroma, macrophages and other myeloid-derived cells are among the most important players. Since the myeloid cell kinase Hck is highly abundant in the tumour microenvironment and aberrant Hck activation results in spontaneous inflammation of the lung, we are now exploring whether this kinase also supports the growth of tumours.


Quick facts

What roles does inflammation play in cancer?

Cancer cells are able to use the normally healthy process of inflammation to promote their own growth and evade immune detection.

What is a tumour microenvironment?

Within the tumour there are a number of cell types, both cancer cells and non-cancer cell types. This collective of different cell types release proteins and interact, creating a ‘micro’ environment, because of the micro scale at which these cell types co-habituate.

What is a target?

A gene or protein which is identified to cause, or play a major role, in the disease.

What is targeted therapy?

A tailored drug which attacks a specific feature of the cancer. These drugs can be targeted to interfere with signalling within the tumour microenvironment or activate other processes which will kill the cancer cells.

  1. Ernst M and Putoczki TMolecular Pathways: Interleukin 11 as a tumor promoting cytokine – translational implications for cancer. Clin Cancer Research, 2014. 20:5579.    
  2. Phesse TJ, Buchert M, Stuart E, Sterle S, Flanagan DJ, Faux M, Walker F, Zhang H-H, Nowell CJ, Jorissen R, Tan CW, Hirokawa Y, Eissmann M, Poh A, Malaterre J, Pearson HB, Kirsch DG, Ramsay RG, Provero P, Poli V, Sieber O, Huszar D, Burgess AW, Vincan E, Ernst M. Partial inhibition of gp130-Jak-Stat3 signaling prevents Wnt-beta-catenin-mediated intestinal tumor growth and regeneration. Science Signaling, 2014. 7(345):ra92.
  3. Stuart E, Buchert M, Putoczki T, Thiem S, Farid R, Elzer J, Huszar D, Waring P, Phesse TJ and Ernst M. Therapeutic inhibition of Jak activity inhibits progression of gastrointestinal tumors in mice. Molecular Cancer Therapy, 2014. 13:468-74.
  4. Putoczki T, Thiem S, Loving A, Busuttil RA, Wilson NJ, Ziegler PL, Nguyen P, Preaudet A, Farid R, Edwards K, Boglev Y, Heath JK, Luwor RB, Jarnicki A, Horst D, Boussioutas A, Sieber O, Pleines I, Kile BT, Nash A, Greten FR, McKenzie BS and Ernst M. Interleukin-11 is the dominant IL-6 family cytokine during gastrointestinal tumorigenesis and can be targeted therapeutically. Cancer Cell, 2013.  24:257-271.
  5. Thiem S, Pierce TP, Palmieri M, Putoczki TL, Buchert M, Preaudet A, Farid RO, Love C, Catimel B, Lei Z, Rozen S, Gopalakrishnan V, Schaper F, Hallek M, Boussioutas A, Tan P, Jarnicki A and Ernst M. mTORC1 inhibition restricts inflammation-associated gastrointestinal tumorigenesis in mice. J Clin Invest, 2013. 123:767-781.

For a complete list of Matthias Ernst's publications, click here.

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