更新于：2024-11-01

ARF6 x RAS

更新于：2024-11-01

基本信息

关联

项与 ARF6 x RAS 相关的药物

Rasarfin

靶点

ARF6 x RAS

作用机制

ARF6 inhibitors [+1]

在研机构

McGill University

原研机构

McGill University

在研适应症

肿瘤

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 ARF6 x RAS 相关的临床结果

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100 项与 ARF6 x RAS 相关的转化医学

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0 项与 ARF6 x RAS 相关的专利（医药）

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项与 ARF6 x RAS 相关的文献（医药）

2024-10-18·Science Advances

Semaphorin 3D promotes pancreatic ductal adenocarcinoma progression and metastasis through macrophage reprogramming

Article

作者: Ibanez, Hector E ; Jaffee, Elizabeth M ; Funes, Vanessa ; Dwayne L Thomas Ii ; Kolodkin, Alex ; Sun, Wei-Chih ; Davuluri, Sanjana ; Henderson, MacKenzie ; Fujiwara, Kenji ; Fu, Juan ; Thompson, Elizabeth ; Muth, Stephen ; Thielman, Noelle R J ; Teh, Selina Shiqing ; Pan, Xingyi ; Zhu, Qingfeng ; Meng, Fengxi ; Zheng, Lei ; Li, Keyu

Axon guidance molecules are frequently altered in pancreatic ductal adenocarcinoma (PDA) and influence PDA progression. However, the molecular mechanism remained unclear. Using genetically engineered mouse models to examine semaphorin 3D (SEMA3D), we identified a dual role for tumor- and nerve-derived SEMA3D in the malignant transformation of pancreatic epithelial cells and invasive PDA development. Pancreatic-specific knockout of the SEMA3D gene from the KRAS G12D and TP53 R172H mutation knock-in, PDX1-Cre(KPC) mouse model demonstrated delayed tumor initiation, prolonged survival, absence of metastasis, and reduced M2 macrophage expression. Mechanistically, tumor- and nerve-derived SEMA3D indirectly reprograms macrophages through KRAS MUT -dependent ARF6 signaling in PDA cells, resulting in increased lactate production, which is sensed by GPCR132 on macrophages to stimulate protumorigenic M2 polarization. Multiplex immunohistochemistry demonstrated increased M2-polarized macrophages proximal to nerves in SEMA3D-expressing human PDA tissue. This study suggests that altered SEMA3D expression leads to an acquisition of cancer-promoting functions, and nerve-derived SEMA3D is “hijacked” by PDA cells to support growth and metastasis in a KRAS MUT -dependent manner.

2023-12-01·Non-coding RNA Research

miR-624 accelerates the growth of liver cancer cells by inhibiting EMC3

Article

作者: Lu, Dongdong ; Wang, Liyan ; Xie, Sijie ; Chen, Yingji ; Li, Shujie ; Song, Shuting ; Liu, Xinlei ; Lu, Yi ; Jiang, Xiaoxue

miRNA is a noncoding RNA found in recent years and more than one third of human genes are the target of miRNAs. miR-624, located on human chromosome 14, is associated with tumorigenesis. However, the role of miR-624 in human hepatocarcinogenesis is still unclear. Herein, our results indicate that miR-624 accelerates the growth of liver cancer cells in vivo and in vitro. Moreover, the modification distribution of H3K9me1 on chromosomes is different between rLV group and rLV-miR-624 group. miR-624 affects epigenetic regulation of several genes in human liver cancer cells, such as RAB21, SMARCD3, MAPK6,PRRX1, ZFHX3, EMC3 (TMEM111). Furthermore, miR-624 affects transcriptome of some genes in liver cancer, including RAB21， UBE2N， PPP1CC，KPNA3， RAB7A，CPEB2,KLF4， MARK2， JUN， ARF6， TMEM39A. On the other hand, miR-624 affects proteome of several genes in liver cancer, such as, RBM5,PTK2, KDM2A,POLR2H, POLR2G,CDK6,KIF15,CUL2,FKBP2,ErbB-3,JUN, PKM2, CyclinE,PLK1, mTOR, PPARγ, Rab7A,ARAF, UPF3B ，PTEN, SUZ12, GADD45, H3.3, CUL5, ARF6,EMC3,ATG4B,ATG14,CALR. Interestingly, miR-624 affects the RAB7A interaction network in liver cancer cells, involving in CLTC，ITGB1，HNRNPU， DARS1， RPS16， CTPS1，H3-3B，JUN,MYH10， CUL5， CPSF7. Strikingly, excessive MEC3 abrogates the carcinogenic functions of miR-624. Importantly, our findings indicate that miR-624 affects some signaling pathway in liver cancer, including Wnt signaling pathway，Hippo signaling pathway，mTOR signaling pathway, Ras signaling pathway，MAPK signaling pathway，PI3K-Akt signaling pathway, erbB signaling pathway. These results provide a basis for the treatment of human liver cancer.

2023-10-01·Acta pharmaceutica Sinica. B

Arf6 as a therapeutic target: Structure, mechanism, and inhibitors.

Review

作者: Chen, Lixia ; Sun, Dejuan ; Li, Hua ; Guo, Yuanyuan ; Tang, Piyu

ADP-ribosylation factor 6 (Arf6), a small G-protein of the Ras superfamily, plays pivotal roles in multiple cellular events, including exocytosis, endocytosis, actin remodeling, plasma membrane reorganization and vesicular transport. Arf6 regulates the progression of cancer through the activation of cell motility and invasion. Aberrant Arf6 activation is a potential therapeutic target. This review aims to understand the comprehensive function of Arf6 for future cancer therapy. The Arf6 GEFs, protein structure, and roles in cancer have been summarized. Comprehending the mechanism underlying Arf6-mediated cancer cell growth and survival is essential. The structural features of Arf6 and its efforts are discussed and may be contributed to the discovery of future novel protein-protein interaction inhibitors. In addition, Arf6 inhibitors and mechanism of action are listed in the table. This review further emphasizes the crucial roles in drug resistance and attempts to offer an outlook of Arf6 in cancer therapy.