Hypoxia-inducible factor 1α regulates lung adenocarcinoma cell invasion

Kou Gi Shyu, Feng Lin Hsu, Ming Jen Wang, Bao Wei Wang, Shankung Lin

Research output: Contribution to journalArticle

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Abstract

We studied the role of hypoxia-inducible factor-1α (HIF-1α) in human lung adenocarcinoma cell invasion using a metastatic cell model composed of low invasive CL1 and highly invasive CL1-5 cells. We showed that HIF-1α was expressed in CL1-5 but not in CL1 cells under normoxic condition, and that inhibition of HIF-1α expression by a small interfering RNA decreased invasiveness of CL1-5 cells. Complementary, overexpression of HIF-1α increased the invasiveness of CL1 and gastric cancer SC-M1 cells. Subsequently, we showed that urokinase-type plasminogen activator receptor (uPAR), and matrix metalloproteinases (MMPs) 1 and 2 were critical in HIF-1α-induced invasion. Mechanistic studies revealed that HIF-1α overexpression could increase the expression of uPAR and MMP1, but not MMP2. However, ELISA assays on the conditioned media generated from control CL1 and CL1 cells overexpressing HIF-1α showed that overexpression of HIF-1α increased the levels of endogenous free active MMP2 and total free MMP2, and the former was blocked by inhibition of MMP1 expression. We conclude that (i) HIF-1α overexpression enhances lung cancer cell invasion at least through up-regulating the expression and activities of uPAR, MMP1, and MMP2; and (ii) induction of MMP1 participates in cell invasion and also plays an important role in HIF-1α-induced activation of MMP2.

Original languageEnglish
Pages (from-to)1181-1191
Number of pages11
JournalExperimental Cell Research
Volume313
Issue number6
DOIs
Publication statusPublished - Apr 1 2007

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Hypoxia-Inducible Factor 1
Urokinase Plasminogen Activator Receptors
Adenocarcinoma of lung
Cell Hypoxia
Matrix Metalloproteinase 1
Matrix Metalloproteinase 2
Conditioned Culture Medium
Small Interfering RNA
Stomach Neoplasms
Lung Neoplasms
Enzyme-Linked Immunosorbent Assay

Keywords

  • HIF-1α
  • Lung adenocarcinoma
  • Metastasis
  • MMP

ASJC Scopus subject areas

  • Cell Biology

Cite this

Hypoxia-inducible factor 1α regulates lung adenocarcinoma cell invasion. / Shyu, Kou Gi; Hsu, Feng Lin; Wang, Ming Jen; Wang, Bao Wei; Lin, Shankung.

In: Experimental Cell Research, Vol. 313, No. 6, 01.04.2007, p. 1181-1191.

Research output: Contribution to journalArticle

Shyu, Kou Gi ; Hsu, Feng Lin ; Wang, Ming Jen ; Wang, Bao Wei ; Lin, Shankung. / Hypoxia-inducible factor 1α regulates lung adenocarcinoma cell invasion. In: Experimental Cell Research. 2007 ; Vol. 313, No. 6. pp. 1181-1191.
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