Division of Life Sciences, Korea University, Seoul, South Korea.
FASEB J. 2019 Mar;33(3):4248-4260. doi: 10.1096/fj.201802018R. Epub 2018 Dec 6.
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.
细胞外囊泡包含各种参与肿瘤生长、转移和免疫逃逸的细胞成分。细胞外囊泡分为 2 组，即外泌体和微泡（MV）。尽管已经研究了外泌体的形成和作用，但 MV 的确切功能和 MV 释放的机制尚不完全清楚。我们发现表皮生长因子通过诱导 NF-κB 激活和 CD133 表达来加速 MV 从质膜释放。发现出芽 MV 的数量和大小取决于 CD133 的表达水平，CD133 调节小 GTP 酶 RhoA 和 Rac1 的活性。从 KRAS 突变结肠癌细胞释放的含有 CD133 的 MV 将 KRAS 突变体递送到相邻的非致瘤细胞，并激活 KRAS 下游信号。发现含有 CD133 的 MV 促进了相邻细胞的迁移和侵袭。含有 CD133 的 MV 通过消除抗表皮生长因子受体（EGFR）药物对结肠癌细胞增殖和运动的抑制作用，导致化学耐药性的发展。这些结果表明 CD133 作为 MV 释放和癌蛋白转运的新型调节剂发挥作用。CD133 可以作为治疗抗 EGFR 药物耐药性结肠癌的靶点。-Kang，M.，Kim，S.，Ko，J. CD133 在结肠癌细胞中 MV 形成和癌蛋白转运中的作用。
