Related Experiment Video
Updated: Jun 18, 2025
12:06
Isolation of CD133+ Liver Stem Cells for Clonal Expansion
Published on: October 10, 2011
22.4K
KCTD17-mediated Ras stabilization promotes hepatocellular carcinoma progression
Young Hoon Jung1,2,3, Yun Ji Lee1,2,3, Tam Dao4
1Department of Biomedical Sciences, College of Medicine, Inha University, Incheon, Korea.
Clinical and Molecular Hepatology
|August 4, 2024
Summary
Potassium channel tetramerization domain containing 17 (KCTD17) protein promotes hepatocellular carcinoma (HCC) by stabilizing Ras. Inhibiting KCTD17 with antisense oligonucleotides reduced tumor growth in mice, suggesting KCTD17 as a potential HCC therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Potassium channel tetramerization domain containing 17 (KCTD17) is an adaptor for the cullin3 (Cul3) ubiquitin ligase complex.
- KCTD17's role in hepatocellular carcinoma (HCC) pathogenesis is not well understood.
- This study investigates KCTD17's clinical features and mechanistic impact on HCC progression.
Purpose of the Study:
- To elucidate the clinical features of KCTD17 in HCC.
- To investigate the molecular mechanisms by which KCTD17 influences HCC progression.
- To evaluate KCTD17-directed therapies for HCC.
Main Methods:
- Analysis of transcriptomic data from HCC patients.
- Assessment of HCC progression in hepatocyte-specific KCTD17 deficient mice treated with diethylnitrosamine (DEN).
- In vivo testing of KCTD17-directed antisense oligonucleotides (ASO) in a mouse model of HCC.
Main Results:
- KCTD17 expression is upregulated in HCC tumors and mouse models.
- KCTD17 targets leucine zipper-like transcriptional regulator 1 (Lztr1) for degradation, stabilizing Ras and promoting liver cancer cell proliferation, migration, and wound healing.
- KCTD17 deficiency or ASO treatment reduced HCC carcinogenesis, tumor growth, and Ras protein levels.
Conclusions:
- KCTD17 stabilizes Ras and downstream signaling pathways, driving HCC progression.
- KCTD17 represents a potential novel therapeutic target for hepatocellular carcinoma.
- Targeting KCTD17 with ASOs demonstrates therapeutic potential in preclinical HCC models.
More Related Videos
06:51Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer
Published on: July 21, 2018
17.9K
12:24A Three-Dimensional Spheroid Model to Investigate the Tumor-Stromal Interaction in Hepatocellular Carcinoma
Published on: September 30, 2021
5.1K
Related Concept Videos
02:38The Ras Gene
6.2K
The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a...
Ras is a...
6.2K
01:07MAPK Signaling Cascades
5.3K
Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
5.3K
02:23Abnormal Proliferation
4.5K
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.5K
03:03mTOR Signaling and Cancer Progression
3.8K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
3.8K
02:07Tumor Progression
6.3K
Tumor progression is a phenomenon where the pre-formed tumor acquires successive mutations to become clinically more aggressive and malignant. In the 1950s, Foulds first described the stepwise progression of cancer cells through successive stages.
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
6.3K
01:24Small GTPases - Ras and Rho
3.9K
Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
Three regulatory proteins control their activity:
3.9K