Lysophosphatidic acid stimulates PC-3 prostate cancer cell matrigel invasion through activation of RhoA and NF-κB activity

Young Sun Hwang, Jennelle C. Hodge, Neela Sivapurapu, Paul F. Lindholm

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

This study was performed to determine the relationship of lysophosphatidic acid (LPA) stimulation and increased Ras homolog A (RhoA) activity to nuclear factor kappa B (NF-κB) activity, and the role of these factors in regulating prostate cancer cell invasion. PC-3 high invasive cells demonstrated constitutively increased RhoA, NF-κB, and in vitro Matrigel invasion which were further induced by LPA stimulation or transfection with constitutively active RhoA Q63E mutant. LPA treatment rapidly and transiently induced RhoA activity followed by maximally increased DNA binding of NF-κB at 1 h and AP-1 at 4 h. The LPA-induced NF-κB DNA binding was preceded by transient IκBα phosphorylation, and decreased total IκBα levels. Further demonstrating the relationship between RhoA and NF-κB activation, PC-3 cells stably transfected with constitutively active RhoA Q63E demonstrated constitutively increased phospho-IκBα, while PC-3 cells transfected with dominant negative RhoA N19 exhibited decreased phospho-IκBα levels. The LPA-induced Matrigel invasion and NF-κB DNA binding activity were both inhibited by expression of the RhoA inhibitor C3 exoenzyme or dominant negative mutant NF-κB inhibitor IκBα S32/36A. Similarly, transfection with dominant negative IκBα S32/36A inhibited PC-3 RhoA Q63E cell in vitro invasion. Treatment of PC-3 high invasive and RhoA Q63E cells with sodium salicylate or lactacystin inhibited NF-κB and invasion, while pyrrolidine dithiocarbamate (PDTC) treatment of PC-3 high invasive cells inhibited NF-κB only. Each inhibitor blocked LPA-induced invasion while PDTC inhibited LPA-induced NF-κB and invasion to the greatest extent. These results point to a model where LPA stimulates RhoA and increased PC-3 prostate cancer cell invasion activity through an NF-κB-dependent pathway.

Original languageEnglish (US)
Pages (from-to)518-529
Number of pages12
JournalMolecular Carcinogenesis
Volume45
Issue number7
DOIs
StatePublished - Jul 2006
Externally publishedYes

Fingerprint

NF-kappa B
Prostatic Neoplasms
Transfection
DNA
lysophosphatidic acid
matrigel
Sodium Salicylate
Transcription Factor AP-1
Phosphorylation

Keywords

  • Invasion
  • Lysophosphatidic acid
  • NF-κB
  • Prostate
  • RhoA

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Biology

Cite this

Lysophosphatidic acid stimulates PC-3 prostate cancer cell matrigel invasion through activation of RhoA and NF-κB activity. / Hwang, Young Sun; Hodge, Jennelle C.; Sivapurapu, Neela; Lindholm, Paul F.

In: Molecular Carcinogenesis, Vol. 45, No. 7, 07.2006, p. 518-529.

Research output: Contribution to journalArticle

Hwang, Young Sun ; Hodge, Jennelle C. ; Sivapurapu, Neela ; Lindholm, Paul F. / Lysophosphatidic acid stimulates PC-3 prostate cancer cell matrigel invasion through activation of RhoA and NF-κB activity. In: Molecular Carcinogenesis. 2006 ; Vol. 45, No. 7. pp. 518-529.
@article{175f6d41674a4b1fa90ea7ed02093ae1,
title = "Lysophosphatidic acid stimulates PC-3 prostate cancer cell matrigel invasion through activation of RhoA and NF-κB activity",
abstract = "This study was performed to determine the relationship of lysophosphatidic acid (LPA) stimulation and increased Ras homolog A (RhoA) activity to nuclear factor kappa B (NF-κB) activity, and the role of these factors in regulating prostate cancer cell invasion. PC-3 high invasive cells demonstrated constitutively increased RhoA, NF-κB, and in vitro Matrigel invasion which were further induced by LPA stimulation or transfection with constitutively active RhoA Q63E mutant. LPA treatment rapidly and transiently induced RhoA activity followed by maximally increased DNA binding of NF-κB at 1 h and AP-1 at 4 h. The LPA-induced NF-κB DNA binding was preceded by transient IκBα phosphorylation, and decreased total IκBα levels. Further demonstrating the relationship between RhoA and NF-κB activation, PC-3 cells stably transfected with constitutively active RhoA Q63E demonstrated constitutively increased phospho-IκBα, while PC-3 cells transfected with dominant negative RhoA N19 exhibited decreased phospho-IκBα levels. The LPA-induced Matrigel invasion and NF-κB DNA binding activity were both inhibited by expression of the RhoA inhibitor C3 exoenzyme or dominant negative mutant NF-κB inhibitor IκBα S32/36A. Similarly, transfection with dominant negative IκBα S32/36A inhibited PC-3 RhoA Q63E cell in vitro invasion. Treatment of PC-3 high invasive and RhoA Q63E cells with sodium salicylate or lactacystin inhibited NF-κB and invasion, while pyrrolidine dithiocarbamate (PDTC) treatment of PC-3 high invasive cells inhibited NF-κB only. Each inhibitor blocked LPA-induced invasion while PDTC inhibited LPA-induced NF-κB and invasion to the greatest extent. These results point to a model where LPA stimulates RhoA and increased PC-3 prostate cancer cell invasion activity through an NF-κB-dependent pathway.",
keywords = "Invasion, Lysophosphatidic acid, NF-κB, Prostate, RhoA",
author = "Hwang, {Young Sun} and Hodge, {Jennelle C.} and Neela Sivapurapu and Lindholm, {Paul F.}",
year = "2006",
month = "7",
doi = "10.1002/mc.20183",
language = "English (US)",
volume = "45",
pages = "518--529",
journal = "Molecular Carcinogenesis",
issn = "0899-1987",
publisher = "Wiley-Liss Inc.",
number = "7",

}

TY - JOUR

T1 - Lysophosphatidic acid stimulates PC-3 prostate cancer cell matrigel invasion through activation of RhoA and NF-κB activity

AU - Hwang, Young Sun

AU - Hodge, Jennelle C.

AU - Sivapurapu, Neela

AU - Lindholm, Paul F.

PY - 2006/7

Y1 - 2006/7

N2 - This study was performed to determine the relationship of lysophosphatidic acid (LPA) stimulation and increased Ras homolog A (RhoA) activity to nuclear factor kappa B (NF-κB) activity, and the role of these factors in regulating prostate cancer cell invasion. PC-3 high invasive cells demonstrated constitutively increased RhoA, NF-κB, and in vitro Matrigel invasion which were further induced by LPA stimulation or transfection with constitutively active RhoA Q63E mutant. LPA treatment rapidly and transiently induced RhoA activity followed by maximally increased DNA binding of NF-κB at 1 h and AP-1 at 4 h. The LPA-induced NF-κB DNA binding was preceded by transient IκBα phosphorylation, and decreased total IκBα levels. Further demonstrating the relationship between RhoA and NF-κB activation, PC-3 cells stably transfected with constitutively active RhoA Q63E demonstrated constitutively increased phospho-IκBα, while PC-3 cells transfected with dominant negative RhoA N19 exhibited decreased phospho-IκBα levels. The LPA-induced Matrigel invasion and NF-κB DNA binding activity were both inhibited by expression of the RhoA inhibitor C3 exoenzyme or dominant negative mutant NF-κB inhibitor IκBα S32/36A. Similarly, transfection with dominant negative IκBα S32/36A inhibited PC-3 RhoA Q63E cell in vitro invasion. Treatment of PC-3 high invasive and RhoA Q63E cells with sodium salicylate or lactacystin inhibited NF-κB and invasion, while pyrrolidine dithiocarbamate (PDTC) treatment of PC-3 high invasive cells inhibited NF-κB only. Each inhibitor blocked LPA-induced invasion while PDTC inhibited LPA-induced NF-κB and invasion to the greatest extent. These results point to a model where LPA stimulates RhoA and increased PC-3 prostate cancer cell invasion activity through an NF-κB-dependent pathway.

AB - This study was performed to determine the relationship of lysophosphatidic acid (LPA) stimulation and increased Ras homolog A (RhoA) activity to nuclear factor kappa B (NF-κB) activity, and the role of these factors in regulating prostate cancer cell invasion. PC-3 high invasive cells demonstrated constitutively increased RhoA, NF-κB, and in vitro Matrigel invasion which were further induced by LPA stimulation or transfection with constitutively active RhoA Q63E mutant. LPA treatment rapidly and transiently induced RhoA activity followed by maximally increased DNA binding of NF-κB at 1 h and AP-1 at 4 h. The LPA-induced NF-κB DNA binding was preceded by transient IκBα phosphorylation, and decreased total IκBα levels. Further demonstrating the relationship between RhoA and NF-κB activation, PC-3 cells stably transfected with constitutively active RhoA Q63E demonstrated constitutively increased phospho-IκBα, while PC-3 cells transfected with dominant negative RhoA N19 exhibited decreased phospho-IκBα levels. The LPA-induced Matrigel invasion and NF-κB DNA binding activity were both inhibited by expression of the RhoA inhibitor C3 exoenzyme or dominant negative mutant NF-κB inhibitor IκBα S32/36A. Similarly, transfection with dominant negative IκBα S32/36A inhibited PC-3 RhoA Q63E cell in vitro invasion. Treatment of PC-3 high invasive and RhoA Q63E cells with sodium salicylate or lactacystin inhibited NF-κB and invasion, while pyrrolidine dithiocarbamate (PDTC) treatment of PC-3 high invasive cells inhibited NF-κB only. Each inhibitor blocked LPA-induced invasion while PDTC inhibited LPA-induced NF-κB and invasion to the greatest extent. These results point to a model where LPA stimulates RhoA and increased PC-3 prostate cancer cell invasion activity through an NF-κB-dependent pathway.

KW - Invasion

KW - Lysophosphatidic acid

KW - NF-κB

KW - Prostate

KW - RhoA

UR - http://www.scopus.com/inward/record.url?scp=33745700262&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33745700262&partnerID=8YFLogxK

U2 - 10.1002/mc.20183

DO - 10.1002/mc.20183

M3 - Article

C2 - 16402387

AN - SCOPUS:33745700262

VL - 45

SP - 518

EP - 529

JO - Molecular Carcinogenesis

JF - Molecular Carcinogenesis

SN - 0899-1987

IS - 7

ER -