目的探究Eps15同源结构域蛋白2(Eps15 homology domain-containing protein 2,EHD2)在结肠癌细胞中的作用及其分子机制。方法在SW620细胞系中构建过表达EHD2的细胞模型,检测EMT相关标志分子物的变化,研究过表达EHD2对细胞株的生物学行...目的探究Eps15同源结构域蛋白2(Eps15 homology domain-containing protein 2,EHD2)在结肠癌细胞中的作用及其分子机制。方法在SW620细胞系中构建过表达EHD2的细胞模型,检测EMT相关标志分子物的变化,研究过表达EHD2对细胞株的生物学行为包括转移、侵袭、增殖及凋亡的影响。最后运用异种移植肿瘤模型验证过表达EHD2对裸鼠体内结肠癌的发生及发展的影响。结果过表达EHD2会抑制结肠癌细胞的增殖、迁移、侵袭及促进凋亡;在裸鼠体内,过表达EHD2可以抑制裸鼠皮下肿瘤的生长;且EHD2与EMT相关标志物的表达呈正相关,推测EHD2通过抑制EMT途径抑制结肠癌的进展。结论EHD2可能作为抑癌基因通过EMT进程抑制结肠癌的侵袭和转移。展开更多
The internalization of essential nutrients,lipids and receptors is a crucial process for all eukaryotic cells.Accordingly,endocytosis is highly conserved across cell types and species.Once internalized,small cargocont...The internalization of essential nutrients,lipids and receptors is a crucial process for all eukaryotic cells.Accordingly,endocytosis is highly conserved across cell types and species.Once internalized,small cargocontaining vesicles fuse with early endosomes(also known as sorting endosomes),where they undergo segregation to distinct membrane regions and are sorted and transported on through the endocytic pathway.Although the mechanisms that regulate this sorting are still poorly understood,some receptors are directed to late endosomes and lysosomes for degradation,whereas other receptors are recycled back to the plasma membrane;either directly or through recycling endosomes.The Rab family of small GTP-binding proteins plays crucial roles in regulating these trafficking pathways.Rabs cycle from inactive GDP-bound cytoplasmic proteins to active GTP-bound membraneassociated proteins,as a consequence of the activity of multiple specific GTPase-activating proteins(GAPs) and GTP exchange factors(GEFs).Once bound to GTP,Rabs interact with a multitude of effector proteins that carry out Rab-specific functions.Recent studies have shown that some of these effectors are also interaction partners for the C-terminal Eps15 homology(EHD) proteins,which are also intimately involved in endocytic regulation.A particularly interesting example of common Rab-EHD interaction partners is the MICALlike protein,MICAL-L1.MICAL-L1 and its homolog,MICAL-L2,belong to the larger MICAL family of proteins,and both have been directly implicated in regulating endocytic recycling of cell surface receptors and junctional proteins,as well as controlling cytoskeletal rearrangement and neurite outgrowth.In this review,we summarize the functional roles of MICAL and Rab proteins,and focus on the significance of their interactions and the implications for endocytic transport.展开更多
文摘目的探究Eps15同源结构域蛋白2(Eps15 homology domain-containing protein 2,EHD2)在结肠癌细胞中的作用及其分子机制。方法在SW620细胞系中构建过表达EHD2的细胞模型,检测EMT相关标志分子物的变化,研究过表达EHD2对细胞株的生物学行为包括转移、侵袭、增殖及凋亡的影响。最后运用异种移植肿瘤模型验证过表达EHD2对裸鼠体内结肠癌的发生及发展的影响。结果过表达EHD2会抑制结肠癌细胞的增殖、迁移、侵袭及促进凋亡;在裸鼠体内,过表达EHD2可以抑制裸鼠皮下肿瘤的生长;且EHD2与EMT相关标志物的表达呈正相关,推测EHD2通过抑制EMT途径抑制结肠癌的进展。结论EHD2可能作为抑癌基因通过EMT进程抑制结肠癌的侵袭和转移。
基金Supported by National Natural Science Foundation of China(No.81872372 and No.81902469)2020 Li Ka Shing Foundation Cross-Disciplinary Research Grant(No.2020LKSFG07B)。
基金Supported by The National Institutes of Health grants R01GM074876 (Caplan S and Naslavsky N),R01GM087455 (Caplan S),the Nebraska Dept. of Health (Naslavsky N)P20 RR018759 from the National Center
文摘The internalization of essential nutrients,lipids and receptors is a crucial process for all eukaryotic cells.Accordingly,endocytosis is highly conserved across cell types and species.Once internalized,small cargocontaining vesicles fuse with early endosomes(also known as sorting endosomes),where they undergo segregation to distinct membrane regions and are sorted and transported on through the endocytic pathway.Although the mechanisms that regulate this sorting are still poorly understood,some receptors are directed to late endosomes and lysosomes for degradation,whereas other receptors are recycled back to the plasma membrane;either directly or through recycling endosomes.The Rab family of small GTP-binding proteins plays crucial roles in regulating these trafficking pathways.Rabs cycle from inactive GDP-bound cytoplasmic proteins to active GTP-bound membraneassociated proteins,as a consequence of the activity of multiple specific GTPase-activating proteins(GAPs) and GTP exchange factors(GEFs).Once bound to GTP,Rabs interact with a multitude of effector proteins that carry out Rab-specific functions.Recent studies have shown that some of these effectors are also interaction partners for the C-terminal Eps15 homology(EHD) proteins,which are also intimately involved in endocytic regulation.A particularly interesting example of common Rab-EHD interaction partners is the MICALlike protein,MICAL-L1.MICAL-L1 and its homolog,MICAL-L2,belong to the larger MICAL family of proteins,and both have been directly implicated in regulating endocytic recycling of cell surface receptors and junctional proteins,as well as controlling cytoskeletal rearrangement and neurite outgrowth.In this review,we summarize the functional roles of MICAL and Rab proteins,and focus on the significance of their interactions and the implications for endocytic transport.
