Page 166 - D. Cancer biology
P. 166
[D. Cancer biology-107]
GPR143 regulates the biogenesis of exosomes promotes
cancer metastasis
Yu Jin Lee¹, Kyeong Jin Shin¹, Hyun-Jun Jang¹, Jin-Sun Ryu², Jong Hyuk Yoon⁵, Jeong Kon Seo¹, Yang
Hoon Huh⁴, Sun-Young Kong²˙³, Taejoon Kwon¹, Pann-Ghill Suh¹˙⁵, Young Chan Chae¹
¹School of Life Sciences, Ulsan National Institute of Science and Technology, Ulsan 44919, Republic of Korea,
²Division of Translational Science, Research Institute and Hospital, National Cancer Center, Goyang 10408, Republic
of Korea, ³Department of Cancer Biomedical Science, Graduate School of Cancer Science and Policy, National
Cancer Center, Goyang 10408, Republic of Korea, ⁴Electron Microscopy Research Center, Korea Basic Science
Institute, Cheongju 28119, Republic of Korea, ⁵Korea Brain Research Institute (KBRI), Korea Brain Research
Institute (KBRI), Daegu 41062, Republic of Korea
Exosomes are small vesicles that are secreted by cells and act as mediators of cell to cell communication. Exosomes
support cancer progression and metastasis by transferring bioactive molecules between cancer and various cells in
the local and distant microenvironments. Because of their potential therapeutic significance, important efforts are
being made towards characterizing exosomal contents. However, little is known about the mechanisms that govern
exosome biogenesis. Here we identify GPR143 is highly expressed in several cancer tissues such as breast, prostate,
and melanoma and is associated with poor prognosis in cancer patients. Knockdown or overexpression of GPR143
in cancer cells leads to a decrease or increase of exosome secretion, respectively. Furthermore, knockdown of
GPR143 reduced cancer cell invasiveness and metastasis in vitro and in vivo. At molecular level, GPR143 depletion
decreases multivesicular bodies (MVBs) formation and impairs exosome secretion. GPR143 depletion triggers MVB
co-localization with lysosomes for degradation. These findings may provide a potential therapeutic target to regulate
exosome biogenesis.
