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EGFR and PKC are involved in the activation of ERK1/2 and p90 RSK and the subsequent proliferation of SNU-407 colon cancer cells by muscarinic acetylcholine receptors

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Abstract

We have previously shown that muscarinic acetylcholine receptors (mAChRs) enhance SNU-407 colon cancer cell proliferation via the ERK1/2 pathway. Here, we examined the signaling pathways linking mAChR stimulation to ERK1/2 activation and the subsequent proliferation of SNU-407 cells. The inhibition of the epidermal growth factor receptor (EGFR) by AG1478 or protein kinase C (PKC) by GF109203X significantly reduced carbachol-stimulated ERK1/2 activation and cell proliferation. Cotreatment of the cells with AG1478 and GF109203X produced an additive effect on carbachol-stimulated ERK1/2 activation, suggesting that the EGFR and PKC pathways act in parallel. The p90 ribosomal S6 kinases (RSKs) are downstream effectors of ERK1/2 and are known to have important roles in cell proliferation. In SNU-407 cells, carbachol treatment induced RSK activation in an atropine-sensitive manner, and this RSK activation was decreased by the inhibition of either EGFR or PKC. Moreover, the RSK-specific inhibitor BRD7389 almost completely blocked carbachol-stimulated cell proliferation. Together, these data indicate that EGFR and PKC are involved in mAChR-mediated activation of ERK1/2 and RSK and the subsequent proliferation of SNU-407 colon cancer cells.

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Abbreviations

EGFR:

Epidermal growth factor receptor

ERK1/2:

Extracellular signal-regulated kinases 1 and 2

mAChR:

Muscarinic acetylcholine receptor

MAPK:

Mitogen-activated protein kinase

PKC:

Protein kinase C

PLC:

Phospholipase C

PMA:

Phorbol-12-myristate-13-acetate

RSK:

p90 ribosomal S6 kinase

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Acknowledgments

This work was supported by the Korea Research Foundation grants funded by the Korea Government (KRF-2005-005-J15001 and 2009-0072223) and by the research grant of the Chungbuk National University in 2010.

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Authors and Affiliations

  1. Biotechnology Research Institute, Chungbuk National University, Cheongju, 361-763, Korea

    Yang-Seo Park

  2. Department of Biochemistry, College of Natural Sciences, Chungbuk National University, Cheongju, 361-763, Korea

    Nam Jeong Cho

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Correspondence to Nam Jeong Cho.

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Park, YS., Cho, N.J. EGFR and PKC are involved in the activation of ERK1/2 and p90 RSK and the subsequent proliferation of SNU-407 colon cancer cells by muscarinic acetylcholine receptors. Mol Cell Biochem 370, 191–198 (2012). https://doi.org/10.1007/s11010-012-1410-z

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  • DOI: https://doi.org/10.1007/s11010-012-1410-z

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