Snail1 induced in breast cancer cells in 3D collagen I gel environment suppresses cortactin and impairs effective invadopodia formation

Mi Sook Lee, Sudong Kim, Baek Gil Kim, Cheolhee Won, Seo Hee Nam, Suki Kang, Hye Jin Kim, Minkyung Kang, Jihye Ryu, Haeng Eun Song, Doohyung Lee, Sang Kyu Ye, Noo Li Jeon, Tai Young Kim, Namhoon Cho, Jung Weon Lee

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Although an in vitro 3D environment cannot completely mimic the in vivo tumor site, embedding tumor cells in a 3D extracellular matrix (ECM) allows for the study of cancer cell behaviors and the screening of anti-metastatic reagents with a more in vivo-like context. Here we explored the behaviors of MDA-MB-231 breast cancer cells embedded in 3D collagen I. Diverse tumor environmental conditions (including cell density, extracellular acidity, or hypoxia as mimics for a continuous tumor growth) reduced JNKs, enhanced TGFβ1/Smad signaling activity, induced Snail1, and reduced cortactin expression. The reduced JNKs activity blocked efficient formation of invadopodia labeled with actin, cortactin, or MT1-MMP. JNKs inactivation activated Smad2 and Smad4, which were required for Snail1 expression. Snail1 then repressed cortactin expression, causing reduced invadopodia formation and prominent localization of MT1-MMP at perinuclear regions. MDA-MB-231 cells thus exhibited less efficient collagen I degradation and invasion in 3D collagen I upon JNKs inhibition. These observations support a signaling network among JNKs, Smads, Snail1, and cortactin to regulate the invasion of MDA-MB-231 cells embedded in 3D collagen I, which may be targeted during screening of anti-invasion reagents.

Original languageEnglish
Pages (from-to)2037-2054
Number of pages18
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1843
Issue number9
DOIs
Publication statusPublished - 2014 Jan 1

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Cortactin
Collagen
Gels
Breast Neoplasms
Matrix Metalloproteinase 14
Neoplasms
Extracellular Matrix
Actins
Cell Count
Podosomes
Growth

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

Cite this

Lee, Mi Sook ; Kim, Sudong ; Kim, Baek Gil ; Won, Cheolhee ; Nam, Seo Hee ; Kang, Suki ; Kim, Hye Jin ; Kang, Minkyung ; Ryu, Jihye ; Song, Haeng Eun ; Lee, Doohyung ; Ye, Sang Kyu ; Jeon, Noo Li ; Kim, Tai Young ; Cho, Namhoon ; Lee, Jung Weon. / Snail1 induced in breast cancer cells in 3D collagen I gel environment suppresses cortactin and impairs effective invadopodia formation. In: Biochimica et Biophysica Acta - Molecular Cell Research. 2014 ; Vol. 1843, No. 9. pp. 2037-2054.
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title = "Snail1 induced in breast cancer cells in 3D collagen I gel environment suppresses cortactin and impairs effective invadopodia formation",
abstract = "Although an in vitro 3D environment cannot completely mimic the in vivo tumor site, embedding tumor cells in a 3D extracellular matrix (ECM) allows for the study of cancer cell behaviors and the screening of anti-metastatic reagents with a more in vivo-like context. Here we explored the behaviors of MDA-MB-231 breast cancer cells embedded in 3D collagen I. Diverse tumor environmental conditions (including cell density, extracellular acidity, or hypoxia as mimics for a continuous tumor growth) reduced JNKs, enhanced TGFβ1/Smad signaling activity, induced Snail1, and reduced cortactin expression. The reduced JNKs activity blocked efficient formation of invadopodia labeled with actin, cortactin, or MT1-MMP. JNKs inactivation activated Smad2 and Smad4, which were required for Snail1 expression. Snail1 then repressed cortactin expression, causing reduced invadopodia formation and prominent localization of MT1-MMP at perinuclear regions. MDA-MB-231 cells thus exhibited less efficient collagen I degradation and invasion in 3D collagen I upon JNKs inhibition. These observations support a signaling network among JNKs, Smads, Snail1, and cortactin to regulate the invasion of MDA-MB-231 cells embedded in 3D collagen I, which may be targeted during screening of anti-invasion reagents.",
author = "Lee, {Mi Sook} and Sudong Kim and Kim, {Baek Gil} and Cheolhee Won and Nam, {Seo Hee} and Suki Kang and Kim, {Hye Jin} and Minkyung Kang and Jihye Ryu and Song, {Haeng Eun} and Doohyung Lee and Ye, {Sang Kyu} and Jeon, {Noo Li} and Kim, {Tai Young} and Namhoon Cho and Lee, {Jung Weon}",
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Lee, MS, Kim, S, Kim, BG, Won, C, Nam, SH, Kang, S, Kim, HJ, Kang, M, Ryu, J, Song, HE, Lee, D, Ye, SK, Jeon, NL, Kim, TY, Cho, N & Lee, JW 2014, 'Snail1 induced in breast cancer cells in 3D collagen I gel environment suppresses cortactin and impairs effective invadopodia formation', Biochimica et Biophysica Acta - Molecular Cell Research, vol. 1843, no. 9, pp. 2037-2054. https://doi.org/10.1016/j.bbamcr.2014.05.007

Snail1 induced in breast cancer cells in 3D collagen I gel environment suppresses cortactin and impairs effective invadopodia formation. / Lee, Mi Sook; Kim, Sudong; Kim, Baek Gil; Won, Cheolhee; Nam, Seo Hee; Kang, Suki; Kim, Hye Jin; Kang, Minkyung; Ryu, Jihye; Song, Haeng Eun; Lee, Doohyung; Ye, Sang Kyu; Jeon, Noo Li; Kim, Tai Young; Cho, Namhoon; Lee, Jung Weon.

In: Biochimica et Biophysica Acta - Molecular Cell Research, Vol. 1843, No. 9, 01.01.2014, p. 2037-2054.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Snail1 induced in breast cancer cells in 3D collagen I gel environment suppresses cortactin and impairs effective invadopodia formation

AU - Lee, Mi Sook

AU - Kim, Sudong

AU - Kim, Baek Gil

AU - Won, Cheolhee

AU - Nam, Seo Hee

AU - Kang, Suki

AU - Kim, Hye Jin

AU - Kang, Minkyung

AU - Ryu, Jihye

AU - Song, Haeng Eun

AU - Lee, Doohyung

AU - Ye, Sang Kyu

AU - Jeon, Noo Li

AU - Kim, Tai Young

AU - Cho, Namhoon

AU - Lee, Jung Weon

PY - 2014/1/1

Y1 - 2014/1/1

N2 - Although an in vitro 3D environment cannot completely mimic the in vivo tumor site, embedding tumor cells in a 3D extracellular matrix (ECM) allows for the study of cancer cell behaviors and the screening of anti-metastatic reagents with a more in vivo-like context. Here we explored the behaviors of MDA-MB-231 breast cancer cells embedded in 3D collagen I. Diverse tumor environmental conditions (including cell density, extracellular acidity, or hypoxia as mimics for a continuous tumor growth) reduced JNKs, enhanced TGFβ1/Smad signaling activity, induced Snail1, and reduced cortactin expression. The reduced JNKs activity blocked efficient formation of invadopodia labeled with actin, cortactin, or MT1-MMP. JNKs inactivation activated Smad2 and Smad4, which were required for Snail1 expression. Snail1 then repressed cortactin expression, causing reduced invadopodia formation and prominent localization of MT1-MMP at perinuclear regions. MDA-MB-231 cells thus exhibited less efficient collagen I degradation and invasion in 3D collagen I upon JNKs inhibition. These observations support a signaling network among JNKs, Smads, Snail1, and cortactin to regulate the invasion of MDA-MB-231 cells embedded in 3D collagen I, which may be targeted during screening of anti-invasion reagents.

AB - Although an in vitro 3D environment cannot completely mimic the in vivo tumor site, embedding tumor cells in a 3D extracellular matrix (ECM) allows for the study of cancer cell behaviors and the screening of anti-metastatic reagents with a more in vivo-like context. Here we explored the behaviors of MDA-MB-231 breast cancer cells embedded in 3D collagen I. Diverse tumor environmental conditions (including cell density, extracellular acidity, or hypoxia as mimics for a continuous tumor growth) reduced JNKs, enhanced TGFβ1/Smad signaling activity, induced Snail1, and reduced cortactin expression. The reduced JNKs activity blocked efficient formation of invadopodia labeled with actin, cortactin, or MT1-MMP. JNKs inactivation activated Smad2 and Smad4, which were required for Snail1 expression. Snail1 then repressed cortactin expression, causing reduced invadopodia formation and prominent localization of MT1-MMP at perinuclear regions. MDA-MB-231 cells thus exhibited less efficient collagen I degradation and invasion in 3D collagen I upon JNKs inhibition. These observations support a signaling network among JNKs, Smads, Snail1, and cortactin to regulate the invasion of MDA-MB-231 cells embedded in 3D collagen I, which may be targeted during screening of anti-invasion reagents.

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JF - Biochimica et Biophysica Acta - Molecular Cell Research

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