Increased RAB31 Expression in Cancer-Associated Fibroblasts Promotes Colon Cancer Progression Through HGF-MET Signaling.
Increased RAB31 Expression in Cancer-Associated Fibroblasts Promotes Colon Cancer Progression Through HGF-MET Signaling.
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癌症相关成纤维细胞中 RAB31 表达增加通过 HGF-MET 信号传导促进结肠癌进展
DOI：
10.3389/fonc.2020.01747
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发表时间：
2020
影响因子：
4.7
通讯作者：
Kefeng D
中科院分区：
文献类型：
--
作者：
Yang T;Zhiheng H;Zhanhuai W;Qian X;Yue L;Xiaoxu G;Jingsun W;Shu Z;Kefeng D
RAB家族蛋白参与细胞膜的动态调节，在多种肿瘤类型中表达失调，可能改变肿瘤细胞的增殖、迁移和侵袭等生物学特性。我们在前期研究中发现RAS相关蛋白RAB-31(RAB31)在晚期结直肠癌(CRC)中表达增加。RAB31在CRC中的作用从未被研究过。在这项研究中，我们发现RAB31在结肠癌的肿瘤间质中的表达，而不是在癌细胞中的表达，预示着预后不良。RAB31可以在原代癌症相关成纤维细胞(CAF)和配对的正常成纤维细胞中检测到。RAB31高表达CAF的条件培养液(CM)在体内外均能显著促进结肠癌细胞系的迁移。这一过程可能是通过肝细胞生长因子(HGF)的旁分泌作用介导的，在RAB31过表达的CAF的CM中，HGF的分泌增加。药物抑制阻断HGF/MET信号转导通路，阻断RKO中间充质细胞向上皮转化因子(MET)的表达，或抗体中和HGF，均可阻断RAB31表达所介导的RKO细胞迁移。我们认为，在结肠癌中，RAB31在CAF中的表达增加可能通过调节肿瘤间质中HGF的分泌而促进肿瘤的进展。
RAB family proteins participate in the dynamic regulation of cellular membrane compartments and are dysregulated in a variety of tumor types, which may alter the biological properties of cancer cells such as proliferation, migration, and invasion. In our previous study, we found that Ras-related protein Rab-31 (RAB31) expression was increased in late-stage colorectal cancer (CRC). The role of RAB31 has never been investigated in CRC. In this study, we found that expression of RAB31 in the tumor stroma but not cancer cells of colon cancer predicted poor survival. RAB31 can be detected in primary cancer-associated fibroblasts (CAFs) and paired normal fibroblasts. Conditioned medium (CM) from RAB31 overexpressing CAFs significantly promoted migration of colon cancer cell lines in vitro and in vivo. This process may be mediated by paracrine action of hepatocyte growth factor (HGF), which was increased in the CM of RAB31-overexpressing CAFs. Blockade of HGF/MET signaling by drug inhibition, knockdown of mesenchymal to epithelial transition factor (MET) in RKO, or antibody neutralization of HGF abolished migration of RKO cells mediated by RAB31 expression in CAFs. We propose that in colon cancer, increased RAB31 expression in CAFs may contribute to tumor progression by regulating the secretion of HGF in the tumor stroma.
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SRPX2 和 RAB31 是胰腺癌的有效预后生物标志物
影响因子：
3.9
作者：
Li, Hao;Zhang, Shi-Rong;Wu, Chun-Tao
通讯作者：
Wu, Chun-Tao
影响因子：
3.1
作者：
Hansen, Torben Frostrup;Kjaer-Frifeldt, Sanne;Sorensen, Flemming Brandt
通讯作者：
Sorensen, Flemming Brandt
影响因子：
3.8
作者：
Kotzsch, Matthias;Sieuwerts, Anieta M.;Foekens, John A.
通讯作者：
Foekens, John A.
影响因子：
11.2
作者：
Bertotti, A;Comoglio, PM;Trusolino, L
通讯作者：
Trusolino, L
影响因子：
3.4
作者：
Jögi A;Vaapil M;Johansson M;Påhlman S
通讯作者：
Påhlman S