| RRC ID |
57845
|
| 著者 |
Song Z, Liu T, Chen J, Ge C, Zhao F, Zhu M, Chen T, Cui Y, Tian H, Yao M, Li J, Li H.
|
| タイトル |
HIF-1α-induced RIT1 promotes liver cancer growth and metastasis and its deficiency increases sensitivity to sorafenib.
|
| ジャーナル |
Cancer Lett
|
| Abstract |
Ras-like-without-CAAX-1 (RIT1) belongs to the RAS superfamily of small GTPases, which plays critical roles in tumor progression. However, little is known about the roles of RIT1 in hepatocellular carcinoma (HCC). Here we found that RIT1 expression was positively associated with the presence of intrahepatic metastasis and the histological grade of HCC and higher RIT1 expression indicated shorter overall survival in HCC patients. In vitro and in vivo studies revealed that RIT1 functioned as an oncogene, as overexpression of RIT1 enhanced HCC cell proliferation and aggressive behavior, whereas silencing RIT1 expression repressed the malignant behaviors. Furthermore, RIT1 deficiency increased drug sensitivity to sorafenib treatment. We further demonstrated that hypoxia-inducible factor 1α (HIF-1α) directly transcriptionally upregulated RIT1, and its stableness was positively correlated with RIT1 expression in HCC tissues. Knockdown of RIT1 attenuated the invasion and migration induced by hypoxia. Collectively, our data highlight the significance of HIF-1α/RIT1 axis in driving HCC progression and sorafenib resistance.
|
| 巻・号 |
460
|
| ページ |
96-107
|
| 公開日 |
2019-9-28
|
| DOI |
10.1016/j.canlet.2019.06.016
|
| PII |
S0304-3835(19)30377-5
|
| PMID |
31247273
|
| MeSH |
Adult
Aged
Aged, 80 and over
Animals
Antineoplastic Agents / pharmacology*
Carcinoma, Hepatocellular / drug therapy*
Carcinoma, Hepatocellular / genetics
Carcinoma, Hepatocellular / metabolism
Carcinoma, Hepatocellular / secondary
Cell Movement / drug effects*
Cell Proliferation / drug effects*
Drug Resistance, Neoplasm
Female
Gene Expression Regulation, Neoplastic
Hep G2 Cells
Humans
Hypoxia-Inducible Factor 1, alpha Subunit / genetics
Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
Liver Neoplasms / drug therapy*
Liver Neoplasms / genetics
Liver Neoplasms / metabolism
Liver Neoplasms / pathology
Male
Mice, Inbred BALB C
Mice, Nude
Middle Aged
Neoplasm Invasiveness
Signal Transduction
Sorafenib / pharmacology*
Xenograft Model Antitumor Assays
Young Adult
ras Proteins / genetics
ras Proteins / metabolism*
|
| IF |
7.36
|
| 引用数 |
4
|
| リソース情報 |
| ヒト・動物細胞 |
HuH-7 |
