Nadja Katheder and collaborators in the lab of Tor Erik Rusten, the Department of Molecular Cell Biology, and CCB has 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 findings have been subject to news coverage by the Norwegian national broadcasting corporation (NRK).
The prestigious journal "Developmental Cell" has recently published an article in their "Previews" section, entitled "Breaking Down Neighbors to Fuel Tumorigenesis". Here, the authors discuss how the work of Katheder and colleagues "opens new avenues for understanding and manipulating cancers through cell-cell communication."
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. This is halted upon genetic or pharmacological intervention of autophagy in the microenvironment or reducing transport of amino acids to tumor cells.
|Team at Centre for Cancer Biomedicine behind the study
Front row from left: Rojyar Khezri, Nadja Sandra Katheder, Fergal O'Farrell.
2nd row: Ashish Jain, Tor Erik Rusten, Andreas Brech, Sebastian Schultz.
3rd row: Kay Oliver Schink, Theodossis A. Theodossiou, Harald Stenmark.
Click on image to enlarge.
Click on scientist links for individual publication lists.
The Nature article:
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 Jan 11
The Previews article in Developmental Cell:
The findings have gained nation-wide attention.
From Norwegian media:
From NRK (Norwegian Broadcasting Corporation):
Kreftceller lurer friske celler til selvmord (translated to: "Cancer cells trick healthy cells into suicide")
From the University of Oslo news section:
Cancer cells grow by exploiting their neighbours
Kreftceller utnytter nabohjelp for å vokse
Link collection will be continually updated (last update February 10th)
|First author Nadja Katheder and senior author Tor Erik Rusten (click to enlarge)|