KCl cotransport is an important modulator of human cervical cancer growth and invasion

Meng-Ru Shen, Cheng-Yang Chou, Keng-Fu Hsu, Yueh Mei Hsu, Wen-Tai Chiu, Ming-Jer Tang, Seth L. Alper, J. Clive Ellory

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

Cervical cancer is a major world health problem for women, but the pathophysiology of this disease has received scant attention. Here we show that the growth and invasion of cervical cancer cells are strongly linked the expression and activity of the KCl cotransporter (KCC), an important regulator of the ionic and cellular osmotic homeostasis. Functional assays of KCl cotransport activation by osmotic swelling, staurosporine, and N-ethylmaleimide indicate that removal of the N-terminal 117 amino acids from KCC1 produces a dominant-negative loss-of-function phenotype for KCl cotransport in human cervical cancer cells. The capability for regulatory volume decrease is much attenuated in the loss-of-function KCC mutant cervical cancer cells. The loss-of-function KCC mutant cervical cancer cells exhibit inhibited cell growth accompanied by decreased activity of the cell cycle gene products retinoblastoma and cdc2 kinase. Reduced cellular invasiveness is in parallel by reduced expression of αvβ3 and α 6β4 integrins, accompanied by decreased activity of matrix metalloproteinase 2 and 9. Inhibition of tumor growth in SCID mice confirms the crucial role of KCC in promoting cervical cancer growth and invasion. Thus, blockade of KCl cotransport may be a useful therapeutic adjunctive strategy to retard or prevent cervical cancer invasion.

Original languageEnglish
Pages (from-to)39941-39950
Number of pages10
JournalJournal of Biological Chemistry
Volume278
Issue number41
DOIs
Publication statusPublished - 2003 Oct 10

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Uterine Cervical Neoplasms
Modulators
Cells
Growth
Ethylmaleimide
Staurosporine
Matrix Metalloproteinase 2
Matrix Metalloproteinase 9
Cell growth
Medical problems
Integrins
Activity Cycles
cdc Genes
Swelling
Tumors
Assays
SCID Mice
Retinoblastoma
Phosphotransferases
Genes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

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title = "KCl cotransport is an important modulator of human cervical cancer growth and invasion",
abstract = "Cervical cancer is a major world health problem for women, but the pathophysiology of this disease has received scant attention. Here we show that the growth and invasion of cervical cancer cells are strongly linked the expression and activity of the KCl cotransporter (KCC), an important regulator of the ionic and cellular osmotic homeostasis. Functional assays of KCl cotransport activation by osmotic swelling, staurosporine, and N-ethylmaleimide indicate that removal of the N-terminal 117 amino acids from KCC1 produces a dominant-negative loss-of-function phenotype for KCl cotransport in human cervical cancer cells. The capability for regulatory volume decrease is much attenuated in the loss-of-function KCC mutant cervical cancer cells. The loss-of-function KCC mutant cervical cancer cells exhibit inhibited cell growth accompanied by decreased activity of the cell cycle gene products retinoblastoma and cdc2 kinase. Reduced cellular invasiveness is in parallel by reduced expression of αvβ3 and α 6β4 integrins, accompanied by decreased activity of matrix metalloproteinase 2 and 9. Inhibition of tumor growth in SCID mice confirms the crucial role of KCC in promoting cervical cancer growth and invasion. Thus, blockade of KCl cotransport may be a useful therapeutic adjunctive strategy to retard or prevent cervical cancer invasion.",
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KCl cotransport is an important modulator of human cervical cancer growth and invasion. / Shen, Meng-Ru; Chou, Cheng-Yang; Hsu, Keng-Fu; Hsu, Yueh Mei; Chiu, Wen-Tai; Tang, Ming-Jer; Alper, Seth L.; Ellory, J. Clive.

In: Journal of Biological Chemistry, Vol. 278, No. 41, 10.10.2003, p. 39941-39950.

Research output: Contribution to journalArticle

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AU - Shen, Meng-Ru

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AU - Hsu, Keng-Fu

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