Related Experiment Video
Updated: May 8, 2025
Modeling Spontaneous Metastatic Renal Cell Carcinoma mRCC in Mice Following Nephrectomy
Published on: April 29, 2014
ACE Loss Drives Renal Cell Carcinoma Growth and Invasion by Modulating AKT-FOXO1
Lei Yin1,2,3, Lixin Mao4, Rui Yin5
1Department of Urology, Shidong Hospital, Yangpu District, Shidong Hospital Affiliated to University of Shanghai for Science and Technology, Shanghai, 200438, People's Republic of China.
Purpose:
Emerging literature links the role of the renin-angiotensin-aldosterone system (RAAS) to the progression of cancers. However, the function of RAAS has not been verified in Clear-cell renal cell carcinoma (ccRCC).
Methods:
ACE expression in ccRCC tissues was determined using RT-PCR, Western blot, and immunohistochemistry staining. The clinical significance of ACE was evaluated through Cox regression analysis. To assess the impact of ACE expression on ccRCC cell growth, metastasis, and glucose activity, CCK-8 assays, transwell assays, Seahorse detection, and xenograft models were utilized. The mechanisms of ACE and its upstream and downstream regulatory factors were investigated using RNA-seq, chromatin immunoprecipitation (ChIP), and luciferase reporter assays.
Results:
RAAS-related gene Angiotensin-Converting Enzyme (ACE) was significantly under expressed in ccRCC cells and tissues. High ACE expression was positively associated with a favorable prognosis in ccRCC patients. Functional studies showed that ACE overexpression suppressed ccRCC cell line OS-RC-2 and A498 growth, metastasis, and glycolysis activities, while its knockdown had the opposite effect. Mechanistically, ACE inhibited ccRCC progression and epithelial-mesenchymal transition (EMT) by disrupting the AKT-FOXO1 signaling pathway. Furthermore, we provide evidence that ACE could enhance everolimus (approved agent for ccRCC) antitumor effect and ACE expression is transcriptionally regulated by ZBTB26.
Conclusion:
Our findings investigated the roles and mechanisms of ACE in ccRCC. ACE inhibits the growth and metastasis of ccRCC cells in vitro and in vivo by promoting FOXO1 expression, which is the downstream target of PI3K-AKT pathway. Thus, this research suggests that ACE may be a promising target for new therapeutic strategy in ccRCC.
Insights
Angiotensin-Converting Enzyme (ACE) is underexpressed in clear-cell renal cell carcinoma (ccRCC). Higher ACE levels correlate with better ccRCC prognosis and inhibit tumor growth and metastasis by regulating the AKT-FOXO1 pathway, suggesting ACE as a therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- The renin-angiotensin-aldosterone system (RAAS) is implicated in cancer progression.
- The specific role of RAAS in clear-cell renal cell carcinoma (ccRCC) remains unverified.
Purpose of the Study:
- To investigate the expression and function of Angiotensin-Converting Enzyme (ACE), a key RAAS component, in ccRCC.
- To elucidate the underlying mechanisms of ACE in ccRCC progression and its potential as a therapeutic target.
Main Methods:
- Quantitative RT-PCR, Western blot, and immunohistochemistry for ACE expression analysis.
- Cell proliferation, migration, invasion, and glycolysis assays (CCK-8, Transwell, Seahorse).
- Xenograft models, RNA-seq, ChIP, and luciferase reporter assays to explore molecular mechanisms.
Main Results:
- ACE was significantly underexpressed in ccRCC tissues and cell lines.
- High ACE expression was associated with favorable patient prognosis.
- ACE overexpression suppressed ccRCC cell growth, metastasis, and glycolysis, while knockdown enhanced these processes.
- ACE inhibited ccRCC progression and epithelial-mesenchymal transition (EMT) via the AKT-FOXO1 signaling pathway.
- ACE enhanced the antitumor effect of everolimus and its expression is regulated by ZBTB26.
Conclusions:
- ACE plays an inhibitory role in ccRCC progression, growth, and metastasis.
- ACE exerts its effects by promoting FOXO1 expression, a downstream target of the PI3K-AKT pathway.
- ACE represents a potential therapeutic target for ccRCC treatment.
More Related Videos
11:13Author Spotlight: Exploring Salidroside's Molecular Mechanisms in Breast Cancer Treatment
Published on: June 9, 2023
06:00Development of a Human Preclinical Model of Osteoclastogenesis from Peripheral Blood Monocytes Co-cultured with Breast Cancer Cell Lines
Published on: September 13, 2017
Related Concept Videos
03:03mTOR Signaling and Cancer Progression
The mTOR pathway or the...
01:22PI3K/mTOR/AKT Signaling Pathway
01:20The Retinoblastoma Gene
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
01:12Loss of Tumor Suppressor Gene Functions
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
02:34Inhibition of Cdk Activity
02:53Adaptive Mechanisms in Cancer Cells
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...