scholarly journals Meprinα Transactivates the Epidermal Growth Factor Receptor (EGFR) via Ligand Shedding, thereby Enhancing Colorectal Cancer Cell Proliferation and Migration

2012 ◽  
Vol 287 (42) ◽  
pp. 35201-35211 ◽  
Author(s):  
Petra Minder ◽  
Elke Bayha ◽  
Christoph Becker-Pauly ◽  
Erwin E. Sterchi
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Cancer Progression ◽  
Cell Proliferation And Migration ◽  
Epidermal Growth ◽  
Colorectal Cancer Progression ◽  
And Migration ◽  
Proliferation And Migration

Meprinα, an astacin-type metalloprotease is overexpressed in colorectal cancer cells and is secreted in a non-polarized fashion, leading to the accumulation of meprinα in the tumor stroma. The transition from normal colonocytes to colorectal cancer correlates with increased meprinα activity at primary tumor sites. A role for meprinα in invasion and metastatic dissemination is supported by its pro-angiogenic and pro-migratory activity. In the present study, we provide evidence for a meprinα-mediated transactivation of the EGFR signaling pathway and suggest that this mechanism is involved in colorectal cancer progression. Using alkaline phosphatase-tagged EGFR ligands and an ELISA assay, we demonstrate that meprinα is capable of shedding epidermal growth factor (EGF) and transforming growth factor-α (TGFα) from the plasma membrane. Shedding was abrogated using actinonin, an inhibitor for meprinα. The physiological effects of meprinα-mediated shedding of EGF and TGFα were investigated with human colorectal adenocarcinoma cells (Caco-2). Proteolytically active meprinα leads to an increase in EGFR and ERK1/2 phosphorylation and subsequently enhances cell proliferation and migration. In conclusion, the implication of meprinα in the EGFR/MAPK signaling pathway indicates a role of meprinα in colorectal cancer progression.

scholarly journals MiR-629-5p promotes colorectal cancer progression through targetting CXXC finger protein 4

2018 ◽  
Vol 38 (4) ◽  
Author(s):  
Jinlai Lu ◽  
Shuirong Lu ◽  
Jingze Li ◽  
Qi Yu ◽  
Lang Liu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Cancer Progression ◽  
Cell Apoptosis ◽  
Tumor Promoter ◽  
Finger Protein ◽  
Cell Proliferation And Migration ◽  
Colorectal Cancer Progression ◽  
And Migration ◽  
Proliferation And Migration

MiR-629-5p has been shown to function as a tumor promoter in some types of cancer. However, the role of miR-629-5p in colorectal cancer remains unclear. Here, the significant up-regulation of miR-629-5p in colorectal cancer tissues and cell lines was observed. Overexpression of miR-629-5p showed a positive effect on cell proliferation and migration. The enhanced miR-629-5p level also suppressed cell apoptosis and resulted in a low Bax level and a high Bcl-2 level. Further down-regulating miR-629-5p demonstrated opposite effects. CXXC finger protein 4 (CXXC4) was predicted as a direct target of miR-629-5p. Dual-luciferase reporter and Western blotting assays exhibited miR-629-5p directly bound to the 3′UTR of CXXC4 and then down-regulated its expression at post-transcriptional level. CXXC4 knockdown rescued the decreased cell proliferation and migration and the enhanced cell apoptosis induced by inhibiting miR-629-5p expression. Notably, overexpression of miR-629-5p also conferred 5-fluorouracil sensitivity, which was partly abrogated by coexpression of CXXC4. Overall, the results presented here suggest that miR-629-5p functions as a tumor promoter by improving proliferation and migration and repressing apoptosis and 5-FU sensitivity in colorectal cancer progression by directly down-regulating CXXC4.

Requirement of the epidermal growth factor receptor in renal epithelial cell proliferation and migration

2004 ◽  
Vol 287 (3) ◽  
pp. F365-F372 ◽  
Author(s):  
Shougang Zhuang ◽  
Yujing Dang ◽  
Rick G. Schnellmann
Keyword(s):  
Cell Proliferation ◽  
Epidermal Growth Factor Receptor ◽  
Cell Migration ◽  
Growth Factor ◽  
Growth Factor Receptor ◽  
Mechanical Injury ◽  
Cell Proliferation And Migration ◽  
Epidermal Growth ◽  
And Migration ◽  
Proliferation And Migration

We showed that renal proximal tubular cells (RPTC) can proliferate and migrate following plating and oxidant or mechanical injury in the absence of exogenous growth factors; however, the mechanisms of this response remain unclear. We examined whether epidermal growth factor receptor (EGFR) signaling is activated following plating and mechanical injury and mediates RPTC proliferation and migration. EGFR, Akt [a target of phosphoinositide-3-kinase (PI3K)], and ERK1/2 were activated after plating and mechanical injury, and their phosphorylation was further enhanced by addition of exogenous EGF. Inactivation of the EGFR with the selective inhibitor AG-1478 completely blocked phosphorylation of EGFR, Akt, and ERK1/2 and blocked cell proliferation and migration after plating and injury. Inhibition of PI3K with LY-294002 blocked Akt phosphorylation and proliferation, whereas U-0126 blocked ERK1/2 phosphorylation but had no effect on proliferation. Furthermore, p38 was phosphorylated following mechanical injury and the p38 inhibitor SB-203580 blocked p38 phosphorylation and cell migration. In contrast, neither PI3K nor ERK1/2 inhibition blocked cell migration. These results show that EGFR activation is required for RPTC proliferation and migration and that proliferation is mediated by PI3K, whereas migration is mediated by p38.

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