STIM1-dependent Ca2+ signaling regulates podosome formation to facilitate cancer cell invasion

Yun-Wen Chen, Yih Fung Chen, Wen Tai Chiu, Hong Chen Chen, Meng Ru Shen

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

The clinical significance of STIM proteins and Orai Ca2+ channels in tumor progression has been demonstrated in different types of cancers. Podosomes are dynamic actin-rich cellular protrusions that facilitate cancer cell invasiveness by degrading extracellular matrix. Whether STIM1-dependent Ca2+ signaling facilitates cancer cell invasion through affecting podosome formation remains unclear. Here we show that the invasive fronts of cancer tissues overexpress STIM1, accompanied by active store-operated Ca2+ entry (SOCE). Interfering SOCE activity by SOCE inhibitors and STIM1 or Orai1 knockdown remarkably affects podosome rosettes formation. Mechanistically, STIM1-silencing significantly alters the podosome rosettes dynamics, shortens the maintenance phase of podosome rosettes and reduces cell invasiveness. The subsequently transient expression of STIM1 cDNA in STIM1-null (STIM1-/-) mouse embryo fibroblasts rescues the suppression of podosome formation, suggesting that STIM1-mediated SOCE activation directly regulates podosome formation. This study uncovers SOCE-mediated Ca2+ microdomain that is the molecular basis for Ca2+ sensitivity controlling podosome formation.

Original languageEnglish
Article number11523
JournalScientific reports
Volume7
Issue number1
DOIs
Publication statusPublished - 2017 Dec 1

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Neoplasms
Cell Surface Extensions
Rosette Formation
Podosomes
Extracellular Matrix
Actins
Embryonic Structures
Complementary DNA
Fibroblasts
Maintenance
Proteins

All Science Journal Classification (ASJC) codes

  • General

Cite this

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abstract = "The clinical significance of STIM proteins and Orai Ca2+ channels in tumor progression has been demonstrated in different types of cancers. Podosomes are dynamic actin-rich cellular protrusions that facilitate cancer cell invasiveness by degrading extracellular matrix. Whether STIM1-dependent Ca2+ signaling facilitates cancer cell invasion through affecting podosome formation remains unclear. Here we show that the invasive fronts of cancer tissues overexpress STIM1, accompanied by active store-operated Ca2+ entry (SOCE). Interfering SOCE activity by SOCE inhibitors and STIM1 or Orai1 knockdown remarkably affects podosome rosettes formation. Mechanistically, STIM1-silencing significantly alters the podosome rosettes dynamics, shortens the maintenance phase of podosome rosettes and reduces cell invasiveness. The subsequently transient expression of STIM1 cDNA in STIM1-null (STIM1-/-) mouse embryo fibroblasts rescues the suppression of podosome formation, suggesting that STIM1-mediated SOCE activation directly regulates podosome formation. This study uncovers SOCE-mediated Ca2+ microdomain that is the molecular basis for Ca2+ sensitivity controlling podosome formation.",
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STIM1-dependent Ca2+ signaling regulates podosome formation to facilitate cancer cell invasion. / Chen, Yun-Wen; Chen, Yih Fung; Chiu, Wen Tai; Chen, Hong Chen; Shen, Meng Ru.

In: Scientific reports, Vol. 7, No. 1, 11523, 01.12.2017.

Research output: Contribution to journalArticle

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AU - Shen, Meng Ru

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