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Updated: May 11, 2026

A Genetically Engineered Mouse Model of Sporadic Colorectal Cancer
Published on: July 6, 2017
The role of ERK2 in colorectal carcinogenesis is partly regulated by TRAPPC4
Yu-Rong Weng1, Xuan Kong, Ya-Nan Yu
1Division of Gastroenterology and Hepatology, Renji Hospital,Shanghai Jiao-Tong University School of Medicine, Shanghai Institute of Digestive Disease, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, State Key Laboratory of Oncogene and Related Genes, Shanghai, China.
Abstract:
The extracellular signal-regulated kinase (ERK), mitogen-activated protein kinase (MAPK) pathway is an important cell proliferation pathway. We previously reported that the transport protein particle complex 4 (TRAPPC4), ERK2 interaction may activate ERK1/2, modulate pERK2 nuclear localization and regulate proliferation and apoptosis in colorectal cancer (CRC) cells. The present study further investigated the function of the TRAPPC4-ERK2 interaction in CRC in vitro and in vivo. Silencing of TRAPPC4 induced G0/G1 phase cell cycle arrest, upregulated p21 and downregulated cyclin B1 in CRC cells. Overexpression of TRAPPC4 after ERK2 silencing decreased the percentage of G0/G1 phase cells, increased the percentage of G2/M and S phase cells, downregulated p21, upregulated cyclin B1, and enhanced CRC cell viability. Immunohistochemical staining revealed that knockdown of TRAPPC4 downregulated pERK2, whereas overexpression of TRAPPC4 upregulated pERK2. Epidermal growth factor (EGF) stimulated upregulation of TRAPPC4 and pERK2 in SW1116 cells; EGF stimulation or overexpression of TRAPPC4 induced pERK2 nuclear translocation. Silencing of TRAPPC4 reduced SW1116 xenograft tumor growth in vivo, whereas overexpression of TRAPPC4 increased tumor growth, compared to control tumors. Moreover, modulation of TRAPPC4 expression in vivo affected the levels of pERK2 in the cytoplasm and nucleus and expression of p21. These results conclusively demonstrate that TRAPPC4 regulates ERK2 activation and also affects the distribution of activated pERK2 in CRC cells. The ability of ERK2 to play a role in colorectal carcinogenesis depends, at least in part, on TRAPPC4.
Insights
Transport protein particle complex 4 (TRAPPC4) regulates colorectal cancer (CRC) cell proliferation by modulating the ERK2 pathway. TRAPPC4 influences cell cycle progression and tumor growth, highlighting its role in colorectal carcinogenesis.
Area of Science:
- Molecular Biology
- Cell Biology
- Cancer Research
Background:
- The extracellular signal-regulated kinase (ERK) pathway is crucial for cell proliferation.
- Previous work suggested TRAPPC4-ERK2 interaction activates ERK1/2 and influences colorectal cancer (CRC) cell behavior.
- Further investigation into TRAPPC4-ERK2 function in CRC is warranted.
Purpose of the Study:
- To investigate the role of TRAPPC4-ERK2 interaction in colorectal cancer (CRC) progression.
- To elucidate how TRAPPC4 modulates ERK2 activation, localization, and downstream effects on cell cycle and viability in CRC.
Main Methods:
- TRAPPC4 gene silencing and overexpression in CRC cells.
- Cell cycle analysis (G0/G1, G2/M, S phases) and viability assays.
- Immunohistochemistry for pERK2, Western blotting for p21 and cyclin B1.
- In vivo xenograft studies in mice.
Main Results:
- TRAPPC4 modulation affected cell cycle distribution (G0/G1 arrest or progression) and CRC cell viability.
- TRAPPC4 influenced pERK2 levels and nuclear translocation, particularly upon EGF stimulation.
- TRAPPC4 knockdown reduced tumor growth in vivo, while overexpression increased it.
- TRAPPC4 expression levels correlated with pERK2 and p21 expression in vivo.
Conclusions:
- TRAPPC4 is a key regulator of ERK2 activation and its subcellular distribution in CRC cells.
- TRAPPC4 plays a significant role in colorectal carcinogenesis by influencing the ERK2 pathway.
- Targeting TRAPPC4 may offer a therapeutic strategy for colorectal cancer.
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