Both ERK and Wnt/β-catenin pathways are involved in Wnt3a-induced proliferation

Mi Sun Yun, Sung Eun Kim, Soung Hoo Jeon, Jung Soo Lee, Kang Yell Choi

Research output: Contribution to journalArticle

148 Citations (Scopus)

Abstract

The Wnt family of proteins regulates development and cell growth. We identified Wnt3a-based regulatory mechanisms for cell proliferation in NIH3T3 fibroblast cells. The degree of Wnt3a-induced proliferation was reduced by β-catenin small interfering RNA (siRNA) and extracellular signal-regulated kinase (ERK) siRNA, indicating that both the ERK and Wnt/β-catenin pathways are involved in Wnt3a-induced proliferation. Wnt3a immediately and transiently activated the Raf-1-MEK-ERK cascade in a manner distinct from that of the β-catenin increase seen in cells treated with Wnt3a. Wnt3a-induced ERK activation was maintained even though basal ERK activities were reduced by β-catenin siRNA, indicating that Wnt3a may activate the ERK pathway independently of β-catenin. The ERK pathway was however, activated by β-catenin transfection, which was abolished by co-transfection with dominant-negative Tcf-4. Therefore, ERK pathway activation by Wnt signaling could occur at multiple levels, including β-catenin-independent direct signaling resulting from a Wnt3a and β-catenin/Tcf-4-dependent post gene transcriptional event. Wnt3a stimulated the G1 to S phase cell cycle progression. This stimulation was reduced by the ERK pathway inhibitor, indicating that Wnt3a promotes proliferation by stimulating the ERK pathway. Wnt3a therefore stimulates the proliferation of fibroblast cells, at least in part, via activation of the ERK and Wnt/β-catenin pathways.

Original languageEnglish
Pages (from-to)313-322
Number of pages10
JournalJournal of Cell Science
Volume118
Issue number2
DOIs
Publication statusPublished - 2005 Jan 15

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Catenins
Wnt Signaling Pathway
Extracellular Signal-Regulated MAP Kinases
Small Interfering RNA
Transfection
Fibroblasts
Wnt Proteins
Cell Proliferation
Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinase Kinases
S Phase
Growth and Development
Cell Cycle

All Science Journal Classification (ASJC) codes

  • Cell Biology

Cite this

Yun, Mi Sun ; Kim, Sung Eun ; Jeon, Soung Hoo ; Lee, Jung Soo ; Choi, Kang Yell. / Both ERK and Wnt/β-catenin pathways are involved in Wnt3a-induced proliferation. In: Journal of Cell Science. 2005 ; Vol. 118, No. 2. pp. 313-322.
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Both ERK and Wnt/β-catenin pathways are involved in Wnt3a-induced proliferation. / Yun, Mi Sun; Kim, Sung Eun; Jeon, Soung Hoo; Lee, Jung Soo; Choi, Kang Yell.

In: Journal of Cell Science, Vol. 118, No. 2, 15.01.2005, p. 313-322.

Research output: Contribution to journalArticle

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