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Updated: Aug 26, 2025

Comparing Metastatic Clear Cell Renal Cell Carcinoma Model Established in Mouse Kidney and on Chicken Chorioallantoic Membrane
Published on: February 8, 2020
SLC18A3 promoted renal cancer development through acetylcholine/cAMP signaling
Peng Tie1, Ji Cheng1, Miao-Xin Xue1
1Department of Urology, Shaanxi Provincial People's Hospital Xi'an, Shaanxi Province, China.
Abstract:
Renal cancer displays a high metastatic potential and a poor response to chemotherapy. However, the critical contributors to renal cancer development remain elusive. This study focused on acetylcholine (ACh) signaling. We identified the vesicular acetylcholine transporter (SLC18A3) that upregulates in patients with renal cancer. We further discovered that SLC18A3 enhanced the uptake of ACh, a classical neurotransmitter mediating synaptic transmission. The elevated ACh activated the protein kinase A (PKA)/cAMP-response element binding protein (CREB) pathway, which contributed to renal cancer cell proliferation and invasive migration. Consistently, SLC18A3 overexpression caused sustained tumor growth and increased lung metastases in A489-bearing mice. In summary, our study demonstrated that SLC18A3 contributed to cancer spread in an ACh/PKA/CREB-dependent manner, which may drive the design of efficacious treatment strategies.
Insights
This study reveals that the vesicular acetylcholine transporter (SLC18A3) promotes renal cancer growth and metastasis by enhancing acetylcholine signaling. Targeting SLC18A3 may offer new treatment strategies for this aggressive cancer.
Area of Science:
- Oncology
- Neuroscience
- Molecular Biology
Background:
- Renal cancer is highly metastatic and chemotherapy-resistant.
- Key drivers of renal cancer development are not fully understood.
- Acetylcholine (ACh) signaling is implicated in cancer progression.
Purpose of the Study:
- To investigate the role of acetylcholine signaling in renal cancer.
- To identify novel molecular targets for renal cancer treatment.
Main Methods:
- Identified SLC18A3 expression in renal cancer patients.
- Investigated the effect of SLC18A3 on ACh uptake and downstream signaling.
- Utilized a mouse model (A489-bearing mice) to assess tumor growth and metastasis.
Main Results:
- SLC18A3 was upregulated in renal cancer patients.
- SLC18A3 enhanced ACh uptake, activating the PKA/CREB pathway.
- SLC18A3 overexpression promoted tumor growth and lung metastasis in mice.
Conclusions:
- SLC18A3 promotes renal cancer progression and metastasis via the ACh/PKA/CREB pathway.
- SLC18A3 represents a potential therapeutic target for renal cancer.
- Findings may guide the development of novel anti-cancer treatments.
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