Netrin secreted by cancer cells: image that acts on different tissues (provided by RIKEN)
Cancer cell secretion “Netrin”: Worsening systemic symptoms!
– RIKEN: Discovery of protein involved in systemic exacerbation of advanced cancer –
As cancer progresses, systemic symptoms worsen, such as weight loss and anorexia.
This condition seen in patients with advanced cancer is called “cancer cachexia.”
“Cancer cachexia” is:
Syndrome is a general term for symptoms associated with the progression of cancer. It adversely affects the prognosis of cancer.
Research into this cancer cachexia has lagged behind. It was a complex disorder involving physiological abnormalities, and there was no analysis method.
Experimental model using Drosophila (RIKEN)
RIKEN (RIKEN): Research Group
In an experimental model using Drosophila, we found that a protein called “netrin” is involved.
It is said that “Netrin” acts on tissues in the body distant from cancer cells, exacerbating systemic symptoms.
How cancer develops:
Currently, various studies are being conducted on the mechanism of cancer development.
However, the treatment results for pancreatic cancer and advanced cancer are still poor.
“Systemic symptoms such as loss of muscle and fat” are observed in more than 80% of patients with advanced cancer.
What is “cachexia”:
The existence of cachexia is also described in ancient Greek medical texts.
It is a translation of the medical term “cachexia”. It was translated in the Meiji period and is still used today.
https://scienceportal.jst.go.jp/gateway/clip/20230606_g01/
Oncogenic stress‐induced Netrin is a humoral signaling molecule that reprograms systemic metabolism in Drosophila
The EMBO Journal：Abstract
Cancer exerts pleiotropic, systemic effects on organisms, leading to health deterioration and eventually to organismal death.
How cancer induces systemic effects on remote organs and the organism itself still remains elusive.
Here we describe a role for NetrinB (NetB), a protein with a particularly well-characterized role as a tissue-level axon guidance cue, in mediating oncogenic stress-induced organismal, metabolic reprogramming as a systemic humoral factor.
In Drosophila, Ras-induced dysplastic cells upregulate and secrete NetB.
Inhibition of either NetB from the transformed tissue or its receptor in the fat body suppresses oncogenic stress-induced organismal death.
NetB from the dysplastic tissue remotely suppresses carnitine biosynthesis in the fat body, which is critical for acetyl-CoA generation and systemic metabolism.
Supplementation of carnitine or acetyl-CoA ameliorates organismal health under oncogenic stress.
This is the first identification, to our knowledge, of a role for the Netrin molecule,
which has been studied extensively for its role within tissues, in humorally mediating systemic effects of local oncogenic stress on remote organs and organismal metabolism.