Axin inhibits extracellular signal-regulated kinase pathway by Ras degradation via beta-catenin
Authors: Kang-Yell Choi
Soung Hoo Jeon
Ju-Yong Yoon
Woo-Jeong Jeong
Sewoon Kim
Young-Nyun Park
Young-Joon Surh
Eek-Hoon Jho
Journal: Journal of Biological Chemistry (2007)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Wnt/beta-catenin pathway; ERK pathway; Axin; Ras; proliferation
Affiliations: National Research Laboratory of Molecular Complex Control, and Department of Biotechnology, Yonsei University, Seoul, Korea.

Abstract:  Interactions between the Wnt/beta-catenin and the extracellular signal-regulated kinase (ERK) pathways have been posited, but the molecular mechanisms and cooperative roles of such interaction in carcinogenesis are poorly understood. In the present study, the Raf-1, MEK, and ERK activities were concomitantly decreased in fibroblasts, which inhibit morphological transformation and proliferation by Axin induction. The inhibition of the components of the ERK pathway by Axin occurred in cells retaining wild-type beta-catenin, including primary hepatocytes, but not in cells retaining non-degradable mutant beta-catenin. Axin inhibits cellular proliferation and ERK pathway activation induced by either epidermal growth factor or Ras, indicating a role of Axin in the regulation of growth induced by ERK pathway activation. ERK pathway regulation by Axin occurs at least partly via reduction of the protein level of Ras. Both wild-type and mutant Ras proteins are subjected to regulation by Axin, which occurs in cells retaining wild-type but not mutant beta-catenin gene. The role of beta-catenin in the regulation of the Ras-ERK pathway was further confirmed by Ras reduction and subsequent inhibitions of the ERK pathway components by knock down of mutated form of beta-catenin. The Ras regulation by Axin was blocked by treatment of leupeptin, an inhibitor of the lysosomal protein degradation machinery. Overall, Axin inhibits proliferation of cells at least partly by reduction of Ras protein level via beta-catenin. This study provides evidences for the role of the Ras-ERK pathway in carcinogenesis caused by mutations of the Wnt/beta-catenin pathway components. 

Retracted: No

PubPeer comments:
 The confocal microscopes in red boxes appear to look similar in Fig 8A and B. ![file] , 
 I also see these two images are same. This study was done SH Jeon more than 15 years, and I also did not notice this up until now. It is possible that he may made a mistake during rearangement of these control data. I will check this matter to him. I appreciate for your careful obervation and notice to me. Thanks again. , 
 I see these two images are same. This study was done by Dr. SH Jeon (shjeon1201@gmail.com more than 15 years, and I also did not notice this at the time of paper submission and up until now. It is possible that he may made a mistake during rearrangement of these control data. I will check this matter to him. I appreciate for your careful observation and notice to me. Thank you for your bring me up with this matter. , 
 I received your suggestion from Professor Kang-yell Choi this morning, and I checked this paper and also, I didn t know this was wrong from the time the paper was submitted. Perhaps there was a mistake during rearrangement process of these image data. Thank you for carefully observing and suggesting this problem. ,