RGD Reference Report - HIF-1α-induced RIT1 promotes liver cancer growth and metastasis and its deficiency increases sensitivity to sorafenib. - Rat Genome Database

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HIF-1α-induced RIT1 promotes liver cancer growth and metastasis and its deficiency increases sensitivity to sorafenib.

Authors: Song, Zhen  Liu, Tengfei  Chen, Jing  Ge, Chao  Zhao, Fangyu  Zhu, Miaoxin  Chen, Taoyang  Cui, Ying  Tian, Hua  Yao, Ming  Li, Jinjun  Li, Hong 
Citation: Song Z, etal., Cancer Lett. 2019 Sep 28;460:96-107. doi: 10.1016/j.canlet.2019.06.016. Epub 2019 Jun 24.
RGD ID: 152999016
Pubmed: PMID:31247273   (View Abstract at PubMed)
DOI: DOI:10.1016/j.canlet.2019.06.016   (Journal Full-text)

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.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
RIT1Humanhepatocellular carcinoma amelioratesIMP human cells in mouse modelRGD 
Rit1Mousehepatocellular carcinoma amelioratesISORIT1 (Homo sapiens)human cells in mouse modelRGD 
Rit1Rathepatocellular carcinoma amelioratesISORIT1 (Homo sapiens)human cells in mouse modelRGD 

Objects Annotated

Genes (Rattus norvegicus)
Rit1  (Ras-like without CAAX 1)

Genes (Mus musculus)
Rit1  (Ras-like without CAAX 1)

Genes (Homo sapiens)
RIT1  (Ras like without CAAX 1)


Additional Information