TY - JOUR
T1 - Identification of EDIL3 on extracellular vesicles involved in breast cancer cell invasion
AU - Lee, Jeong Eun
AU - Moon, Pyong Gon
AU - Cho, Young Eun
AU - Kim, Young Bum
AU - Kim, In San
AU - Park, Hoyong
AU - Baek, Moon Chang
N1 - Funding Information:
This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MEST) ( NRF-2012R1A2A2A01046512 ) and by a grant of the Korean Health Technology R&D project, Ministry of Health & Welfare, Republic of Korea ( HI12C0534 ), and by a grant from the National R&D Program for Cancer Control, Ministry of Health and Welfare, Republic of Korea ( 1420390 ) .
PY - 2016/1/10
Y1 - 2016/1/10
N2 - Cancer cell-derived extracellular vesicles have been linked to the pathogenesis of various cancers; however, the role of extracellular vesicles in tumorigenesis remains unclear. To identify extracellular vesicle proteins involved in cancer metastasis, quantitative proteomic analyses were performed on extracellular vesicles derived from two representative breast cancer cell lines: the less invasive MCF-7 and the invasive MDA-MB-231. Proteomic analysis allowed for the identification of 270 proteins in the extracellular vesicles. Here we report a new function of EDIL3 on extracellular vesicles, which are sufficient for enhancement of cell invasion and for acceleration of lung metastasis in vivo. This invasion is most likely mediated via the integrin-FAK signaling cascade in breast cancer cells. However, these effects are suppressed when EDIL3 is inactivated, providing evidence for a critical role of EDIL3 in development of cancer. Consistently, in human patients with metastatic breast cancer, the levels of EDIL3 on circulating extracellular vesicles are significantly elevated. This information is a remarkable breakthrough in understanding of the molecular mechanism underlying metastasis of breast cancer as well as in the research for cancer biomarkers using circulating extracellular vesicles. Furthermore, targeting EDIL3 on extracellular vesicles may lead to a new therapeutic option for treatment of breast cancer.
AB - Cancer cell-derived extracellular vesicles have been linked to the pathogenesis of various cancers; however, the role of extracellular vesicles in tumorigenesis remains unclear. To identify extracellular vesicle proteins involved in cancer metastasis, quantitative proteomic analyses were performed on extracellular vesicles derived from two representative breast cancer cell lines: the less invasive MCF-7 and the invasive MDA-MB-231. Proteomic analysis allowed for the identification of 270 proteins in the extracellular vesicles. Here we report a new function of EDIL3 on extracellular vesicles, which are sufficient for enhancement of cell invasion and for acceleration of lung metastasis in vivo. This invasion is most likely mediated via the integrin-FAK signaling cascade in breast cancer cells. However, these effects are suppressed when EDIL3 is inactivated, providing evidence for a critical role of EDIL3 in development of cancer. Consistently, in human patients with metastatic breast cancer, the levels of EDIL3 on circulating extracellular vesicles are significantly elevated. This information is a remarkable breakthrough in understanding of the molecular mechanism underlying metastasis of breast cancer as well as in the research for cancer biomarkers using circulating extracellular vesicles. Furthermore, targeting EDIL3 on extracellular vesicles may lead to a new therapeutic option for treatment of breast cancer.
KW - Breast cancer
KW - Cancer biomarker
KW - Cancer invasion
KW - Extracellular vesicles
KW - Integrin-FAK signaling
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U2 - 10.1016/j.jprot.2015.10.005
DO - 10.1016/j.jprot.2015.10.005
M3 - Article
C2 - 26463135
AN - SCOPUS:84948844835
VL - 131
SP - 17
EP - 28
JO - Journal of Proteomics
JF - Journal of Proteomics
SN - 1874-3919
ER -