Homotrimer cavin1 interacts with caveolin1 to facilitate tumor growth and activate microglia through extracellular vesicles in glioma
Homotrimer cavin1 interacts with caveolin1 to facilitate tumor growth and activate microglia through extracellular vesicles in glioma
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同源三聚体cavin1与caveolin1相互作用促进肿瘤生长并通过胶质瘤细胞外囊泡激活小胶质细胞
DOI：
10.7150/thno.45688
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发表时间：
2020-05
期刊：
影响因子：
12.4
通讯作者：
Chunsheng Kang
中科院分区：
文献类型：
--
作者：
Lin Wang;Chao Yang;Qixue Wang;Qi Liu;YUnfei Wang;Junhu Zhou;Yangsheng Li;YanLi Tan;Chunsheng Kang
背景：通过细胞外囊泡（EV）的细胞间通讯在胶质瘤进展中起着关键作用。然而，关于调节EV分泌和功能的精确机制知之甚少。我们的前期研究发现Cavin 1与胶质瘤患者的恶性程度呈正相关，并且胶质瘤细胞中过表达Cavin 1可通过EV增强邻近胶质瘤细胞的恶性程度。研究方法：目前的研究使用生物信息学设计了一种不能与Caveolin 1相互作用的变体Cavin 1（vCavin 1），并比较了胶质瘤细胞中过表达Cavin 1和vCavin 1对EV产生和功能的影响。结果：值得注意的是，我们的结果表明Cavin 1表达增强了胶质瘤源性EV的分泌、摄取和归巢能力。表达Cavin 1的EV在体外和体内促进胶质瘤生长。此外，表达Cavin 1的鼠神经胶质瘤细胞通过EV募集和激活小胶质细胞。然而，vCavin 1既没有加载到EV上，也没有改变EV的分泌和功能。结论：我们的研究结果表明，Cavin 1-Caveolin 1相互作用在调节胶质瘤-EV的产生和功能中起着重要作用，并且可能在表达高水平Cavin 1的胶质瘤中作为有希望的治疗靶点。
Background: Intercellular communication via extracellular vesicles (EVs) plays a critical role in glioma progression. However, little is known about the precise mechanism regulating EV secretion and function. Our previous study revealed that Cavin1 was positively correlated with malignancy grades of glioma patients, and that overexpressing Cavin1 in glioma cells enhanced the malignancy of nearby glioma cells via EVs. Methods: The current study used bioinformatics to design a variant Cavin1 (vCavin1) incapable of interacting with Caveolin1, and compared the effects of overexpressing Cavin1 and vCavin1 in glioma cells on EV production and function. Results: Remarkably, our results indicated that Cavin1 expression enhanced the secretion, uptake, and homing ability of glioma-derived EVs. EVs expressing Cavin1 promoted glioma growth in vitro and in vivo. In addition, Cavin1 expressing murine glioma cells recruited and activated microglia via EVs. However, vCavin1 neither was loaded onto EVs nor altered EV secretion and function. Conclusion: Our findings suggested that Cavin1-Caveolin1 interaction played a significant role in regulating production and function of glioma-EVs, and may act as a promising therapeutic target in gliomas that express high levels of Cavin1.
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DOI：
10.1083/jcb.200302028
发表时间：
2003-05-26
期刊：
The Journal of cell biology
影响因子：
--
作者：
Nabi IR;Le PU
通讯作者：
Le PU
影响因子：
3.7
作者：
Hill MM;Daud NH;Aung CS;Loo D;Martin S;Murphy S;Black DM;Barry R;Simpson F;Liu L;Pilch PF;Hancock JF;Parat MO;Parton RG
通讯作者：
Parton RG
影响因子：
5.3
作者：
Razani, B;Wang, XB;Lisanti, MP
通讯作者：
Lisanti, MP
DOI：
10.1073/pnas.1721434116
发表时间：
2019-01-15
影响因子：
11.1
作者：
Hutter, Gregor;Theruvath, Johanna;Cheshier, Samuel H.
通讯作者：
Cheshier, Samuel H.
影响因子：
--
作者：
Setti M;Osti D;Richichi C;Ortensi B;Del Bene M;Fornasari L;Beznoussenko G;Mironov A;Rappa G;Cuomo A;Faretta M;Bonaldi T;Lorico A;Pelicci G
通讯作者：
Pelicci G