Increased cell survival, migration, invasion, and Akt expression in PTHrP-overexpressing LoVo colon cancer cell lines

Xiaoli Shen, Ramanjaneya V R Mula, B. Mark Evers, Miriam Falzon

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Parathyroid hormone-related protein (PTHrP) has been localized in human colon cancer tissue and cell lines. We have previously shown that PTHrP increases colon cancer cell proliferation, extracellular matrix adhesion, and cell-surface integrin α6β4 expression. Since cancer cell migration, invasion, and survival are crucial components of metastasis, and colon cancer has a high metastatic potential, in this study we used the human colon cancer cell line LoVo as a model system to study the effects of PTHrP on these parameters. PTHrP expression was modulated by stable transfection with a construct expressing PTHrP (- 36 to + 139). We report that PTHrP increases cell migration, invasion, and survival. PTHrP altered cell morphology, with PTHrP-overexpressing cells exhibiting increased spreading and several long protrusions. PTHrP also increased the steady-state mRNA levels of the integrin α6 and β4 subunits, indicating a direct and/or indirect effect of PTHrP on the transcriptional and/or post-transcriptional regulation of integrin α6 and β4 expression. Integrin α6β4 activates the phosphoinositol 3-kinase (PI3-K)/Akt pathway, leading to glycogen synthase kinase-3 (GSK-3) deactivation. PTHrP overexpression also led to an increase in active Akt and inactive GSK-3 levels, indicating that the PTHrP-mediated upregulation of integrin α6β4 expression may activate the PI3-K pathway, resulting in increased cell survival, migration and invasion.

Original languageEnglish (US)
Pages (from-to)61-72
Number of pages12
JournalRegulatory Peptides
Volume141
Issue number1-3
DOIs
StatePublished - Jun 7 2007

Fingerprint

Parathyroid Hormone-Related Protein
Colonic Neoplasms
Cell Movement
Cell Survival
Cells
Cell Line
Integrins
Glycogen Synthase Kinase 3
Phosphotransferases
Cell proliferation
Cell Adhesion
Extracellular Matrix
Transfection
Up-Regulation
Adhesion

Keywords

  • Apoptosis
  • Glycogen synthase kinase-3
  • Integrin α6β4
  • Laminin
  • Parathyroid hormone-related protein

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Physiology
  • Neuroscience(all)

Cite this

Increased cell survival, migration, invasion, and Akt expression in PTHrP-overexpressing LoVo colon cancer cell lines. / Shen, Xiaoli; Mula, Ramanjaneya V R; Evers, B. Mark; Falzon, Miriam.

In: Regulatory Peptides, Vol. 141, No. 1-3, 07.06.2007, p. 61-72.

Research output: Contribution to journalArticle

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