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CAMK2N1 has a cancer-suppressive function in colorectal carcinoma via effects on the Wnt/β-catenin pathway
Xiaolong Zhang1, Lifei Tian1, Zeyu Li1
1Department of General Surgery, Shaanxi Provincial People's Hospital, Xi'an, 710068, China.
Abstract:
The deregulation of calcium/calmodulin-dependent protein kinase II inhibitor 1 (CAMK2N1) is linked to the carcinogenesis reported in several malignancies. To date, studies describing the role of CAMK2N1 in colorectal carcinoma are scarce. The current project was carried out to study the relationship between CAMK2N1 and colorectal carcinoma progression. CAMK2N1 levels were lowered in colorectal carcinoma tissue, which also correlated to poor overall survival in patients. Colorectal carcinoma cell lines with overexpressed CAMK2N1 showed a reduction in transformative phenotypes, including proliferation suppression, the blocking of cell cycle progression, metastasis inhibition and chemoresistance reduction, whereas CAMK2N1-silenced cells showed the opposite effect. Mechanistic studies revealed a novel regulatory role of CAMK2N1 on Wnt/β-catenin transduction. Up-regulation of CAMK2N1 lowered the level of disheveled 2, phosphorylated GSK-3β, β-catenin, c-myc and cyclin D1. Re-expression of β-catenin decreased the CAMK2N1-mediated tumor-inhibiting effects. Moreover, blocking of Wnt/β-catenin diminished CAMK2N1-silencing-elicited cancer-enhancing effect. Critically, the tumorigenicity of CAMK2N1-overexpressed cells was markedly weakened in nude mice. To conclude, the study demonstrated a cancer-suppressive function of CAMK2N1 in colorectal carcinoma and illustrated that CAMK2N1 exerts the tumor-inhibiting effects via suppression of the Wnt/β-catenin pathway.
Insights
Calcium/calmodulin-dependent protein kinase II inhibitor 1 (CAMK2N1) acts as a tumor suppressor in colorectal cancer. Lower CAMK2N1 levels correlate with poor patient survival and promote cancer progression by activating the Wnt/β-catenin pathway.
Area of Science:
- Oncology
- Molecular Biology
Background:
- Deregulation of calcium/calmodulin-dependent protein kinase II inhibitor 1 (CAMK2N1) is implicated in various cancers.
- Limited research exists on CAMK2N1's role in colorectal carcinoma progression.
Purpose of the Study:
- To investigate the relationship between CAMK2N1 expression and colorectal carcinoma progression.
- To elucidate the underlying molecular mechanisms of CAMK2N1's function in colorectal cancer.
Main Methods:
- Analysis of CAMK2N1 levels in colorectal carcinoma tissues and correlation with patient survival.
- In vitro studies using colorectal carcinoma cell lines with CAMK2N1 overexpression and silencing.
- Investigation of CAMK2N1's effect on Wnt/β-catenin pathway components.
- In vivo tumorigenicity assays in nude mice.
Main Results:
- CAMK2N1 levels were significantly decreased in colorectal carcinoma tissues, correlating with poorer overall survival.
- CAMK2N1 overexpression suppressed proliferation, cell cycle progression, metastasis, and chemoresistance.
- CAMK2N1 silencing led to opposite effects, enhancing cancer phenotypes.
- CAMK2N1 negatively regulated the Wnt/β-catenin pathway by reducing levels of key signaling molecules.
- CAMK2N1-mediated tumor inhibition was dependent on Wnt/β-catenin pathway suppression.
- Tumorigenicity of CAMK2N1-overexpressing cells was significantly reduced in vivo.
Conclusions:
- CAMK2N1 exhibits a tumor-suppressive function in colorectal carcinoma.
- CAMK2N1 inhibits colorectal cancer progression primarily through the suppression of the Wnt/β-catenin signaling pathway.
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