Soft substrate up-regulates the interaction of STIM1 with store-operated Ca2+ channels that lead to normal epithelial cell apoptosis

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

We have demonstrated that soft substrate induced apoptosis in polarized cells, but not in transformed cells by disturbance of Ca2+ homeostasis. This study aims to further investigate the regulatory mechanisms underlying the disruption of Ca2+-signaling integrity in soft substrate-induced epithelial apoptosis. Soft substrate up-regulated the store-operated Ca2+ (SOC) entry across the plasma membrane of normal cervical epithelial cells, which resulted in increased cytosolic Ca2+ levels. Concomitantly, soft substrate induced the aggregation and translocation of stromal interacting molecule 1 (STIM1) toward the cell periphery to colocalize with Orai1, an essential pore subunit of SOC channel, detected by fluorescence resonance energy transfer approach and confocal image analyses. The disturbed Ca2+ homeostasis resulted in the activation of μ-calpain, which cleaved α-spectrin, induced actin disorganization, and caused apoptosis. In contrast, soft substrate did not disturb Ca2+ homeostasis or induce apoptosis in cervical cancer cells. Chelating extracellular Ca2+ by EGTA and down-regulated SOC entry by small interfering RNA targeting STIM1 or inhibitors targeting Ca2+-binding site of calpain significantly inhibited soft substrate-induced activation of μ-calpain and epithelial cell apoptosis. Thus, soft substrate up-regulates the interaction of STIM1 with SOC channels, which results in the activation of μ-calpain and subsequently induces normal epithelial cell apoptosis.

Original languageEnglish
Pages (from-to)2220-2230
Number of pages11
JournalMolecular Biology of the Cell
Volume19
Issue number5
DOIs
Publication statusPublished - 2008 May 1

Fingerprint

Calpain
Up-Regulation
Epithelial Cells
Apoptosis
Homeostasis
Spectrin
Fluorescence Resonance Energy Transfer
Egtazic Acid
Uterine Cervical Neoplasms
Small Interfering RNA
Stromal Interaction Molecule 1
Actins
Binding Sites
Cell Membrane

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

Cite this

@article{6c22eb26965f4a45870a17e949750bbf,
title = "Soft substrate up-regulates the interaction of STIM1 with store-operated Ca2+ channels that lead to normal epithelial cell apoptosis",
abstract = "We have demonstrated that soft substrate induced apoptosis in polarized cells, but not in transformed cells by disturbance of Ca2+ homeostasis. This study aims to further investigate the regulatory mechanisms underlying the disruption of Ca2+-signaling integrity in soft substrate-induced epithelial apoptosis. Soft substrate up-regulated the store-operated Ca2+ (SOC) entry across the plasma membrane of normal cervical epithelial cells, which resulted in increased cytosolic Ca2+ levels. Concomitantly, soft substrate induced the aggregation and translocation of stromal interacting molecule 1 (STIM1) toward the cell periphery to colocalize with Orai1, an essential pore subunit of SOC channel, detected by fluorescence resonance energy transfer approach and confocal image analyses. The disturbed Ca2+ homeostasis resulted in the activation of μ-calpain, which cleaved α-spectrin, induced actin disorganization, and caused apoptosis. In contrast, soft substrate did not disturb Ca2+ homeostasis or induce apoptosis in cervical cancer cells. Chelating extracellular Ca2+ by EGTA and down-regulated SOC entry by small interfering RNA targeting STIM1 or inhibitors targeting Ca2+-binding site of calpain significantly inhibited soft substrate-induced activation of μ-calpain and epithelial cell apoptosis. Thus, soft substrate up-regulates the interaction of STIM1 with SOC channels, which results in the activation of μ-calpain and subsequently induces normal epithelial cell apoptosis.",
author = "Wen-Tai Chiu and Ming-Jer Tang and Jao, {Hsiao Chun} and Meng-Ru Shen",
year = "2008",
month = "5",
day = "1",
doi = "10.1091/mbc.E07-11-1170",
language = "English",
volume = "19",
pages = "2220--2230",
journal = "Molecular Biology of the Cell",
issn = "1059-1524",
publisher = "American Society for Cell Biology",
number = "5",

}

TY - JOUR

T1 - Soft substrate up-regulates the interaction of STIM1 with store-operated Ca2+ channels that lead to normal epithelial cell apoptosis

AU - Chiu, Wen-Tai

AU - Tang, Ming-Jer

AU - Jao, Hsiao Chun

AU - Shen, Meng-Ru

PY - 2008/5/1

Y1 - 2008/5/1

N2 - We have demonstrated that soft substrate induced apoptosis in polarized cells, but not in transformed cells by disturbance of Ca2+ homeostasis. This study aims to further investigate the regulatory mechanisms underlying the disruption of Ca2+-signaling integrity in soft substrate-induced epithelial apoptosis. Soft substrate up-regulated the store-operated Ca2+ (SOC) entry across the plasma membrane of normal cervical epithelial cells, which resulted in increased cytosolic Ca2+ levels. Concomitantly, soft substrate induced the aggregation and translocation of stromal interacting molecule 1 (STIM1) toward the cell periphery to colocalize with Orai1, an essential pore subunit of SOC channel, detected by fluorescence resonance energy transfer approach and confocal image analyses. The disturbed Ca2+ homeostasis resulted in the activation of μ-calpain, which cleaved α-spectrin, induced actin disorganization, and caused apoptosis. In contrast, soft substrate did not disturb Ca2+ homeostasis or induce apoptosis in cervical cancer cells. Chelating extracellular Ca2+ by EGTA and down-regulated SOC entry by small interfering RNA targeting STIM1 or inhibitors targeting Ca2+-binding site of calpain significantly inhibited soft substrate-induced activation of μ-calpain and epithelial cell apoptosis. Thus, soft substrate up-regulates the interaction of STIM1 with SOC channels, which results in the activation of μ-calpain and subsequently induces normal epithelial cell apoptosis.

AB - We have demonstrated that soft substrate induced apoptosis in polarized cells, but not in transformed cells by disturbance of Ca2+ homeostasis. This study aims to further investigate the regulatory mechanisms underlying the disruption of Ca2+-signaling integrity in soft substrate-induced epithelial apoptosis. Soft substrate up-regulated the store-operated Ca2+ (SOC) entry across the plasma membrane of normal cervical epithelial cells, which resulted in increased cytosolic Ca2+ levels. Concomitantly, soft substrate induced the aggregation and translocation of stromal interacting molecule 1 (STIM1) toward the cell periphery to colocalize with Orai1, an essential pore subunit of SOC channel, detected by fluorescence resonance energy transfer approach and confocal image analyses. The disturbed Ca2+ homeostasis resulted in the activation of μ-calpain, which cleaved α-spectrin, induced actin disorganization, and caused apoptosis. In contrast, soft substrate did not disturb Ca2+ homeostasis or induce apoptosis in cervical cancer cells. Chelating extracellular Ca2+ by EGTA and down-regulated SOC entry by small interfering RNA targeting STIM1 or inhibitors targeting Ca2+-binding site of calpain significantly inhibited soft substrate-induced activation of μ-calpain and epithelial cell apoptosis. Thus, soft substrate up-regulates the interaction of STIM1 with SOC channels, which results in the activation of μ-calpain and subsequently induces normal epithelial cell apoptosis.

UR - http://www.scopus.com/inward/record.url?scp=48249118684&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=48249118684&partnerID=8YFLogxK

U2 - 10.1091/mbc.E07-11-1170

DO - 10.1091/mbc.E07-11-1170

M3 - Article

VL - 19

SP - 2220

EP - 2230

JO - Molecular Biology of the Cell

JF - Molecular Biology of the Cell

SN - 1059-1524

IS - 5

ER -