The role of ERK2 in colorectal carcinogenesis is partly regulated by TRAPPC4.
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.
['Weng|Yu-Rong|YR|', 'Kong|Xuan|X|', 'Yu|Ya-Nan|YN|', 'Wang|Ying-Chao|YC|', 'Hong|Jie|J|', 'Zhao|Shu-Liang|SL|', 'Fang|Jing-Yuan|JY|']
D000818:Animals D017209:Apoptosis D015153:Blotting, Western D002453:Cell Cycle D002467:Cell Nucleus D049109:Cell Proliferation D015179:Colorectal Neoplasms D004815:Epidermal Growth Factor D006801:Humans D008297:Male D051379:Mice D008807:Mice, Inbred BALB C D008819:Mice, Nude D019950:Mitogen-Activated Protein Kinase 1 D048052:Mitogen-Activated Protein Kinase 3 D020928:Mitogen-Activated Protein Kinases D009419:Nerve Tissue Proteins D010766:Phosphorylation D034741:RNA, Small Interfering D015398:Signal Transduction D015533:Transcriptional Activation D014407:Tumor Cells, Cultured D033921:Vesicular Transport Proteins
cell proliferation cancer cell cycle