TY - JOUR
T1 - Roles of CD133 in microvesicle formation and oncoprotein trafficking in colon cancer
AU - Kang, Minsoo
AU - Kim, Suhyun
AU - Ko, Jesang
N1 - Funding Information:
This work was supported by the Tunneling Nanotube Research Center (NRF-2015R1A5A1009024) through the National Research Foundation of Korea (NRF) grant funded by the Korea government. The authors declare no conflicts of interest.
Publisher Copyright:
© FASEB
PY - 2019/3/1
Y1 - 2019/3/1
N2 - Extracellular vesicles contain various cellular components that are involved in tumor growth, metastasis, and immune escape. Extracellular vesicles are classified into 2 groups, namely, exosomes and microvesicles (MV). Although the formation and roles of exosomes have been studied, the exact functions of MVs and mechanisms underlying MV release are not fully understood. We found that epidermal growth factor accelerates the release of MVs from the plasma membrane by inducing NF-κB activation and CD133 expression. The amount and sizes of budding MVs were found to be dependent on the expression level of CD133, which regulates the activities of the small guanosine 5′-triphosphatases RhoA and Rac1. CD133-containing MVs released from KRAS mutant colon cancer cells delivered KRAS mutant to adjacent nontumorigenic cells and activated KRAS downstream signaling. CD133-containing MVs were found to promote the migration and invasion of adjacent cells. CD133-containing MVs induced the development of chemoresistance by abolishing the inhibitory effects of anti-epidermal growth factor receptor (EGFR) drugs on cell proliferation and motility in colon cancer. These results suggest that CD133 acts as a novel modulator in MV release and in oncoprotein trafficking. CD133 can serve as a therapeutic target for treatment of anti-EGFR drug-resistant colon cancer.—Kang, M., Kim, S., Ko, J. Roles of CD133 in microvesicle formation and oncoprotein trafficking in colon cancer. FASEB J. 33, 4248–4260 (2019). www.fasebj.org.
AB - Extracellular vesicles contain various cellular components that are involved in tumor growth, metastasis, and immune escape. Extracellular vesicles are classified into 2 groups, namely, exosomes and microvesicles (MV). Although the formation and roles of exosomes have been studied, the exact functions of MVs and mechanisms underlying MV release are not fully understood. We found that epidermal growth factor accelerates the release of MVs from the plasma membrane by inducing NF-κB activation and CD133 expression. The amount and sizes of budding MVs were found to be dependent on the expression level of CD133, which regulates the activities of the small guanosine 5′-triphosphatases RhoA and Rac1. CD133-containing MVs released from KRAS mutant colon cancer cells delivered KRAS mutant to adjacent nontumorigenic cells and activated KRAS downstream signaling. CD133-containing MVs were found to promote the migration and invasion of adjacent cells. CD133-containing MVs induced the development of chemoresistance by abolishing the inhibitory effects of anti-epidermal growth factor receptor (EGFR) drugs on cell proliferation and motility in colon cancer. These results suggest that CD133 acts as a novel modulator in MV release and in oncoprotein trafficking. CD133 can serve as a therapeutic target for treatment of anti-EGFR drug-resistant colon cancer.—Kang, M., Kim, S., Ko, J. Roles of CD133 in microvesicle formation and oncoprotein trafficking in colon cancer. FASEB J. 33, 4248–4260 (2019). www.fasebj.org.
KW - KRAS mutant
KW - chemoresistance
KW - extracellular vesicles
UR - http://www.scopus.com/inward/record.url?scp=85079860319&partnerID=8YFLogxK
U2 - 10.1096/fj.201802018R
DO - 10.1096/fj.201802018R
M3 - Article
C2 - 30521383
AN - SCOPUS:85079860319
SN - 1530-6860
VL - 33
SP - 4248
EP - 4260
JO - The FASEB journal : official publication of the Federation of American Societies for Experimental Biology
JF - The FASEB journal : official publication of the Federation of American Societies for Experimental Biology
IS - 3
ER -
