Mechanism for secretion of nano-sized small bags containing substances that cause cancer progression

October 13, 2020

A joint research group of Osaka International Cancer Institute, Kagoshima University, Fujita Health University, RIKEN CSRS, and RIKEN Cluster for Pioneering Research unraveled the mechanism of secretion of small-sized bags (extracellular vesicles = EVs) containing substances that cause cancer progression.

Cancer has been thought to progress with growth and spreading caused by various substances. Recent studies have shown that growth and spreading of cancer are accelerated by spreading of EVs containing the substances from cancer cells through the whole body. Now it is increasingly expected that suppression of the EVs will lead to a treatment method of cancer. Among the several types of EVs with different sizes and components, exosomes are thought to be associated with cancer growth and spreading and have been the focus of research. On the other hand, roles of a different type of EVs (non-exosomal vesicles), which also contains substances involved in the progression of cancer, have not been understood in detail.

The research team found that, in the endoplasmic reticulum in cancer cells, linkage of asparagine (an amino acid, a component of protein) to sugar chain leads to selective production of nonexosomal EVs. By using this mechanism, secretion of this EV can be controlled, which can contribute to cancer treatment.

It has been reported that the linkage of sugar chains to another amino acid, a component of protein, is involved in formation of EVs called microvesicles. With this study, it was shown that conditions of linkage of sugar chains may be one of the universal mechanisms involved in selective production of EVs.

Further understanding of the mechanism by which various EVs are formed should advance the understanding of mechanisms of life phenomena and onset of diseases associated with EVs, and thus contribute to development of treatment for diseases targeting EVs.

Original article
Cell Reports doi:10.1016/j.celrep.2020.108261
Y. Harada, K. Nakajima, T. Suzuki, T. Fukushige, K. Kondo, J. Seino, Y. Ohkawa, T. Suzuki, H. Inoue, T. Kanekura, N. Dohmae, N. Taniguchi, I. Maruyama,
"Glycometabolic regulation of the biogenesis of small extracellular vesicles".
Takehiro Suzuki; Senior Technical Scientist
Naoshi Dohmae; Unit Leader
Biomolecular Characterization Unit