| RRC ID |
67664
|
| 著者 |
Fujii S, Matsumoto S, Nojima S, Morii E, Kikuchi A.
|
| タイトル |
Arl4c expression in colorectal and lung cancers promotes tumorigenesis and may represent a novel therapeutic target.
|
| ジャーナル |
Oncogene
|
| Abstract |
We recently demonstrated that expression of ADP-ribosylation factor (ARF)-like 4c (Arl4c) induced by a combination of Wnt/β-catenin and epidermal growth factor/Ras signaling in normal epithelial cells grown in three-dimensional culture promotes cellular migration and proliferation, resulting in formation of tube-like structures, suggesting the involvement of Arl4c in epithelial morphogenesis. It is conceivable that there could be a common mechanism between epithelial morphogenesis and carcinogenesis. Therefore the current study was conducted to investigate whether Arl4c might be involved in tumorigenesis. Immunohistochemical analyses of tissue specimens obtained from colorectal and lung cancer patients revealed that Arl4c was not observed in non-tumor regions but was strongly expressed at high frequencies in tumor lesions. Inhibition of Wnt/β-catenin or Ras/mitogen-activated protein kinase signaling reduced Arl4c mRNA levels in HCT116 colorectal cancer cells and A549 lung cancer cells. Knockdown of Arl4c inhibited Rac activity and also prevented nuclear localization of yes-associated protein (YAP)/transcriptional co-activator with PDZ-binding motif (TAZ) in these cancer cells. Arl4c-depleted cancer cells consistently showed decreased migration, invasion and proliferation capabilities both in vitro and in vivo. Furthermore, direct injection of Arl4c small interfering RNA (siRNA) into HCT116 cell-derived tumors (in vivo treatment with siRNA) inhibited tumor growth in immunodeficient mice. These results suggest that Arl4c is involved in tumorigenesis and might represent a novel therapeutic target for suppressing proliferation and invasion of colorectal and lung cancer cells.
|
| 巻・号 |
34(37)
|
| ページ |
4834-44
|
| 公開日 |
2015-9-10
|
| DOI |
10.1038/onc.2014.402
|
| PII |
onc2014402
|
| PMID |
25486429
|
| MeSH |
ADP-Ribosylation Factors / antagonists & inhibitors*
ADP-Ribosylation Factors / genetics*
Adenocarcinoma / drug therapy
Adenocarcinoma / genetics*
Adenocarcinoma / pathology
Adult
Aged
Aged, 80 and over
Animals
Cell Transformation, Neoplastic / genetics*
Cell Transformation, Neoplastic / pathology
Colorectal Neoplasms / drug therapy
Colorectal Neoplasms / genetics*
Colorectal Neoplasms / pathology
Gene Expression Regulation, Neoplastic / drug effects
HCT116 Cells
HEK293 Cells
HeLa Cells
Humans
Lung Neoplasms / drug therapy
Lung Neoplasms / genetics*
Lung Neoplasms / pathology
Male
Mice
Mice, Inbred BALB C
Mice, Nude
Middle Aged
Molecular Targeted Therapy*
RNA, Small Interfering / pharmacology
RNA, Small Interfering / therapeutic use
Tumor Cells, Cultured
Xenograft Model Antitumor Assays
|
| IF |
7.971
|
| リソース情報 |
| 遺伝子材料 |
CSII-CMV-MCS-IRES2-Bsd (RDB04385)
CS-RfA-EVBsd (RDB06090)
pCMV-VSV-G-RSV-Rev (RDB04393)
pCAG-HIVgp (RDB04394) |
