Inhibition of protein phosphorylation in MIA pancreatic cancer cells: Confluence of metabolic and signaling pathways

Hengwei Zhang, Rui Cao, Wai Nang Paul Lee, Caishu Deng, Yingchun Zhao, Joan M. Lappe, Robert R. Recker, Yun Yen, Qi Wang, Ming Ying Tsai, Vay Liang Go, Gary Guishan Xiao

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Oxythiamine (OT), a transketolase inhibitor, is known to inhibit pancreatic cancer cell proliferation. In this study, we investigated the effect of inhibition of the transketolase pathway on signaling pathways in MIA PaCa cancer cells using in-house proteomic techniques. We hypothesized that OT alter protein phosphorylation thus affecting cell cycle arrest and cell proliferation. MIA PaCa-2 cells were cultured in media containing an algal 15N amino acid mixture at 50% enrichment, with and without OT, to determine protein expression and synthesis. Analysis of cell lysates using two-dimensional gel electrophoresis matrix assisted laser desorption and ionization time-of-flight and time-of-flight mass spectrometry (2-DE-MALDI-TOF/TOF MS) identified 12 phosphor proteins that were significantly suppressed by OT treatment. Many of these proteins are involved in regulation of cycle activities and apoptosis. Among the proteins identified, expression of the phosphor heat shock protein 27 (Hsp27) was dramatically inhibited by OT treatment while the level of its total protein remained unchanged. Hsp27 expression and phoshporylation is known to be associated with drug resistance and cancer cell survival. The changes in phosphorylation of key proteins of cancer proliferation and survival suggest that protein phosphorylation is the confluence of the effects of OT on metabolic and signaling pathways.

Original languageEnglish
Pages (from-to)980-989
Number of pages10
JournalJournal of Proteome Research
Volume9
Issue number2
DOIs
StatePublished - Feb 5 2010

Fingerprint

Oxythiamine
Phosphorylation
Metabolic Networks and Pathways
Pancreatic Neoplasms
Cells
Proteins
Transketolase
HSP27 Heat-Shock Proteins
Cell proliferation
Phosphors
Cell Proliferation
Activity Cycles
Neoplasms
Matrix-Assisted Laser Desorption-Ionization Mass Spectrometry
Electrophoresis, Gel, Two-Dimensional
Cell Cycle Checkpoints
Electrophoresis
Drug Resistance
Proteomics
Ionization

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Chemistry(all)

Cite this

Inhibition of protein phosphorylation in MIA pancreatic cancer cells : Confluence of metabolic and signaling pathways. / Zhang, Hengwei; Cao, Rui; Lee, Wai Nang Paul; Deng, Caishu; Zhao, Yingchun; Lappe, Joan M.; Recker, Robert R.; Yen, Yun; Wang, Qi; Tsai, Ming Ying; Go, Vay Liang; Xiao, Gary Guishan.

In: Journal of Proteome Research, Vol. 9, No. 2, 05.02.2010, p. 980-989.

Research output: Contribution to journalArticle

Zhang, Hengwei ; Cao, Rui ; Lee, Wai Nang Paul ; Deng, Caishu ; Zhao, Yingchun ; Lappe, Joan M. ; Recker, Robert R. ; Yen, Yun ; Wang, Qi ; Tsai, Ming Ying ; Go, Vay Liang ; Xiao, Gary Guishan. / Inhibition of protein phosphorylation in MIA pancreatic cancer cells : Confluence of metabolic and signaling pathways. In: Journal of Proteome Research. 2010 ; Vol. 9, No. 2. pp. 980-989.
@article{abb23563189b4992941a67e0ae90fe2d,
title = "Inhibition of protein phosphorylation in MIA pancreatic cancer cells: Confluence of metabolic and signaling pathways",
abstract = "Oxythiamine (OT), a transketolase inhibitor, is known to inhibit pancreatic cancer cell proliferation. In this study, we investigated the effect of inhibition of the transketolase pathway on signaling pathways in MIA PaCa cancer cells using in-house proteomic techniques. We hypothesized that OT alter protein phosphorylation thus affecting cell cycle arrest and cell proliferation. MIA PaCa-2 cells were cultured in media containing an algal 15N amino acid mixture at 50{\%} enrichment, with and without OT, to determine protein expression and synthesis. Analysis of cell lysates using two-dimensional gel electrophoresis matrix assisted laser desorption and ionization time-of-flight and time-of-flight mass spectrometry (2-DE-MALDI-TOF/TOF MS) identified 12 phosphor proteins that were significantly suppressed by OT treatment. Many of these proteins are involved in regulation of cycle activities and apoptosis. Among the proteins identified, expression of the phosphor heat shock protein 27 (Hsp27) was dramatically inhibited by OT treatment while the level of its total protein remained unchanged. Hsp27 expression and phoshporylation is known to be associated with drug resistance and cancer cell survival. The changes in phosphorylation of key proteins of cancer proliferation and survival suggest that protein phosphorylation is the confluence of the effects of OT on metabolic and signaling pathways.",
author = "Hengwei Zhang and Rui Cao and Lee, {Wai Nang Paul} and Caishu Deng and Yingchun Zhao and Lappe, {Joan M.} and Recker, {Robert R.} and Yun Yen and Qi Wang and Tsai, {Ming Ying} and Go, {Vay Liang} and Xiao, {Gary Guishan}",
year = "2010",
month = "2",
day = "5",
doi = "10.1021/pr9008805",
language = "English",
volume = "9",
pages = "980--989",
journal = "Journal of Proteome Research",
issn = "1535-3893",
publisher = "American Chemical Society",
number = "2",

}

TY - JOUR

T1 - Inhibition of protein phosphorylation in MIA pancreatic cancer cells

T2 - Confluence of metabolic and signaling pathways

AU - Zhang, Hengwei

AU - Cao, Rui

AU - Lee, Wai Nang Paul

AU - Deng, Caishu

AU - Zhao, Yingchun

AU - Lappe, Joan M.

AU - Recker, Robert R.

AU - Yen, Yun

AU - Wang, Qi

AU - Tsai, Ming Ying

AU - Go, Vay Liang

AU - Xiao, Gary Guishan

PY - 2010/2/5

Y1 - 2010/2/5

N2 - Oxythiamine (OT), a transketolase inhibitor, is known to inhibit pancreatic cancer cell proliferation. In this study, we investigated the effect of inhibition of the transketolase pathway on signaling pathways in MIA PaCa cancer cells using in-house proteomic techniques. We hypothesized that OT alter protein phosphorylation thus affecting cell cycle arrest and cell proliferation. MIA PaCa-2 cells were cultured in media containing an algal 15N amino acid mixture at 50% enrichment, with and without OT, to determine protein expression and synthesis. Analysis of cell lysates using two-dimensional gel electrophoresis matrix assisted laser desorption and ionization time-of-flight and time-of-flight mass spectrometry (2-DE-MALDI-TOF/TOF MS) identified 12 phosphor proteins that were significantly suppressed by OT treatment. Many of these proteins are involved in regulation of cycle activities and apoptosis. Among the proteins identified, expression of the phosphor heat shock protein 27 (Hsp27) was dramatically inhibited by OT treatment while the level of its total protein remained unchanged. Hsp27 expression and phoshporylation is known to be associated with drug resistance and cancer cell survival. The changes in phosphorylation of key proteins of cancer proliferation and survival suggest that protein phosphorylation is the confluence of the effects of OT on metabolic and signaling pathways.

AB - Oxythiamine (OT), a transketolase inhibitor, is known to inhibit pancreatic cancer cell proliferation. In this study, we investigated the effect of inhibition of the transketolase pathway on signaling pathways in MIA PaCa cancer cells using in-house proteomic techniques. We hypothesized that OT alter protein phosphorylation thus affecting cell cycle arrest and cell proliferation. MIA PaCa-2 cells were cultured in media containing an algal 15N amino acid mixture at 50% enrichment, with and without OT, to determine protein expression and synthesis. Analysis of cell lysates using two-dimensional gel electrophoresis matrix assisted laser desorption and ionization time-of-flight and time-of-flight mass spectrometry (2-DE-MALDI-TOF/TOF MS) identified 12 phosphor proteins that were significantly suppressed by OT treatment. Many of these proteins are involved in regulation of cycle activities and apoptosis. Among the proteins identified, expression of the phosphor heat shock protein 27 (Hsp27) was dramatically inhibited by OT treatment while the level of its total protein remained unchanged. Hsp27 expression and phoshporylation is known to be associated with drug resistance and cancer cell survival. The changes in phosphorylation of key proteins of cancer proliferation and survival suggest that protein phosphorylation is the confluence of the effects of OT on metabolic and signaling pathways.

UR - http://www.scopus.com/inward/record.url?scp=76149136025&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=76149136025&partnerID=8YFLogxK

U2 - 10.1021/pr9008805

DO - 10.1021/pr9008805

M3 - Article

C2 - 20035555

AN - SCOPUS:76149136025

VL - 9

SP - 980

EP - 989

JO - Journal of Proteome Research

JF - Journal of Proteome Research

SN - 1535-3893

IS - 2

ER -