Nature article from Nadja Katheder: Microenvironmental autophagy supports tumor growth

Nadja Katheder and collaborators in the lab of Tor Erik Rusten, the Department of Molecular Cell Biology and CCB, have published an article entitled "Microenvironmental autophagy supports tumor growth", in an advanced online publication 11th of January in the journal Nature (journal impact factor 41.46).

The team behind the study at the Centre for Cancer Biomedicine (front from left): Rojyar Khezri, first author Nadja Sandra Katheder, Fergal O'Farrell, (mid from left): Ashish Jain, Tor Erik Rusten, Andreas Brech, Sebastian Schultz, (behind from left): Kay Oliver Schink, Theodossis A. Theodossiou, Harald Stenmark.

It is known that transformed tumor cells rewire growth and metabolism to support their own growth. How these changes occur in animals, however, are poorly understood.

In the published study, Katheder and co-workers show how malignant tumors coerce neighboring microenvironmental cells to support their own growth.

Oncogenic and inflammatory cell signaling in transformed cells act together to reprogram tumor cells to elicit a stress-response, termed autophagy (self eating) in neighboring cells. Studies of autophagy was awarded the Nobel Prize in Physiology or Medicine earlier this year and is best known for shuttling cytoplasmic content to the lysosome for degradation and repurposing of recycled building blocks, like amino acids, nucleotides and fatty acids. In this study, researchers found that pharmacological or genetic inactivation of autophagy specifically in microenvironmental cells, or reducing amino acid import into tumor cells effectively blocked tumor growth and invasion.

The study, supported by Helse Sør Øst and the Norwegian Cancer Society, provides additional impetus to further elucidate the potential for pharmacological intervention of autophagy in cancer treatment. Phase I trials with experimental autophagy intervention is currently being carried out in numerous studies, but so far not in Norway.

Figure:
Friendly neighbors feed tumor cells (Left) Inflammatory and oncogenic signaling in the Cancer Cell (green) coerces neighboring cells of the microenvironment (brown) to produce amino acids by way of autophagy that may be taken up by tumors to support growth. (Right) Malignant tumors of the eye grow and invade the central nervous system killing the animal. Pharmacological or genetic inhibition of autophagy stalls tumor growth and invasion.

Links:
Rusten group of Tumor Host Biology

References:
Microenvironmental autophagy promotes tumour growth
Nadja S. Katheder, Rojyar Khezri, Fergal O’Farrell, Sebastian W. Schultz, Ashish Jain, Mohammed M. Rahman, Kay O. Schink, Theodossis A. Theodossiou, Terje Johansen, Gábor Juhász, David Bilder, Andreas Brech, Harald Stenmark & Tor Erik Rusten
Nature (2017) doi:10.1038/nature20815, Published online 11 January 2017

Nobel Prize in Physiology and Medicine 2016 awarded to studies on Autophagy

Media:
From NRK (Norwegian Broadcasting Corporation): Kreftceller lurer friske celler til selvmord

From University of Oslo news section: Kreftceller utnytter nabohjelp for å vokse

 
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Tor Erik Rusten and Nadja Katheder on NRK1 – Kveldsnytt 11th of January 2017.

Published Jan. 12, 2017 8:27 AM - Last modified Jan. 17, 2017 10:33 AM