Page 165 - D. Cancer biology

[D-107] GPR143 regulates the biogenesis of exosomes

promotes cancer metastasis
1
Yu Jin Lee , Kyeng Jin Shin , Hyun-Jun Jang , Jin-Sun Ryu , Jeong Kon Seo , Yang Hoon Huh ,
3
1
2
1
1
Sun-Young Kong , Taejoon Kwon , and Pann-Ghill Suh and Young Chan Chae ,
1*
1*
2
1
2
1 School of Life Sciences, Ulsan National Institute of Science and Technology, Ulsan 44919 Republic of Korea, Division of Translational Science,
3
Research Institute and Hospital, National Cancer Center, Goyang 10408, Republic of Korea, Electron Microscopy Research Center, Korea Basic
Science Institute, Cheongju-si, Chungcheongbuk-do 28119, Republic of Korea
BACKGROUND
Exosomes are 50-150nm small extracellular vesicles (sEV) that harbor proteins, lipids, RNAs, and DNA, and thereby act as
important mediators of cell-cell communications in various physiological and pathological pathways (1, 2). Cancer-cell-derived
sEV prepare a favorable microenvironment at future metastatic sites as well as the primary tumor. Clinical evidence showing the
direct relationship between exosome levels and metastasis, recurrence, and overall survival of patients with various cancers (3, 4)
suggests that understanding the mechanism underlying exosome biogenesis and secretion in cancer cells can provide new
insights into the development of effective anti-tumor therapeutics.
GPR143, also known to cause ocular albinism type 1 (OA1), is specifically expressed in the pigment cells of the eyes and skin
and is structurally similar to canonical GPCRs (5). However, it dose not show any significant sequence similarity to GPCRs and
thus represents a distinct group of proteins. In addition, GPR143 is localized on the membrane of intracellular organelles such as
late endosomes, lysosomes, and melanosomes (6). GPR143 is involved in eye development, and loss-of-function mutations in
the GPR143 gene cause OA1 (7). Mice lacking GPR143 and OA1 patients with GPR143 mutation exhibit melanosomal
abnormalities, including reduced number, increased size, and abnormal distribution of melanosomes, indicating the GPR143 is
involved in melanosome biogenesis (8). However, the potential roles for GPR143 in cancer progression and in regulating sEV
secretion/biogenesis have yet to be elucidated.
In the present study, we identified the unknown function of GPR143 in cancer progression. Our results reveal the molecular
mechanism underlying exosome biogenesis, thus offering new opportunities for potential therapeutic strategies targeting
metastasis.
RESULTS
A B C
A

D E

B C D

Figure 2. . Roles of GPR143 in promoting breast cancer metastasis
E
A B C

Figure 1. Upregulation of GPR143 correlates with poor patient
survival of Human breast cancer
Figure 3. GPR143 regulates secretion of exosomes in vitro
CONCLUSION REFERENCES ACKNOWLEDGEMENTS

1. Raposo, G & Stoorvogel, W. J. Cell Biol. 200, 373- This research was supported by Basic
• GPR143 is highly expressed in multiple 383 (2013) Science Research Program through the
tumors, especially breast cancer and 2. Colombo M, Raposo G, & Thery C. Annu. Rev. Cell. National Research Foundation of Korea
Dev. Biol. 30: 255-289 (2014)
melanoma. 3. Hoshino A, et al. Nature. 527 (7578) : 329-335 (NRF) funded by the Ministry of Education
• Elevation of GPR143 expression is (2015) (2018R1A6A1A03025810 and NRF-
associated with metastasis progression 4. Kaiser J. Science 352 (6282) : 164-166 (2016) 2019R1I1A1A01061483).
5. Innamorati G. et. al. Pigment Cell Res. 19, 125-135
and patient survival. (2006)
• GPR143 promotes breast cancer 6. Raposo G & Marks M.S. Nat. Rev. Mol. Cell Biol. Contact information
8(10) :786-797 (2007)
metastasis via regulating exosome 7. Cortese k. et al. Invest. Ophthalmol. Vis. Sci. 46
secretion. (12) : 4358-4364 (2005)
8. Schiaffino, M.V. et al. Nat. Genet. 23, 108-112
(1999) ** Yu Jin Lee : yjlee0627@unist.ac.kr