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Expression array analysis of the hepatocyte growth factor invasive program.

Fabiola Cecchi1, Chih-Jian Lih2, Young H Lee1

  • 1Urologic Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892-1501, USA.

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Summary
This summary is machine-generated.

Mouse hepatocyte growth factor (mHGF) and truncated isoforms like NK2 promote prostate cancer cell motility and metastasis through human MET. Gene expression profiling identified key pathways in this HGF invasive program.

Keywords:
Cell migrationHepatocyte growth factorMET receptor tyrosine kinaseProstate cancerSignal transductionTumor metastasis

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Area of Science:

  • Cell Biology
  • Molecular Oncology

Background:

  • Hepatocyte growth factor (HGF) and its receptor MET are crucial for cell growth, movement, and development.
  • Aberrant HGF/MET signaling contributes to cancer progression, including metastasis and angiogenesis.
  • Truncated HGF isoforms (NK1, NK2) and mouse HGF (mHGF) exhibit distinct activities, with mHGF binding human MET.

Purpose of the Study:

  • To investigate the role of mHGF and NK2 in prostate cancer metastasis via human MET.
  • To identify target genes and signaling pathways constituting the HGF invasive program.
  • To correlate gene expression changes with patient survival data.

Main Methods:

  • Gene expression profiling of PC3M prostate cancer cells treated with human HGF (hHGF), NK2, or mHGF.
  • Ingenuity Pathway Analysis (IPA) to identify enriched networks and pathways.
  • Analysis of The Cancer Genome Atlas (TCGA) data for gene co-occurrence and survival correlation.

Main Results:

  • mHGF, similar to NK2, enhanced motility, invasion, and spontaneous metastasis of PC3M cells through human MET.
  • IPA revealed significant overlap between HGF-induced gene expression changes and pathways regulating cell movement and metastasis.
  • A subset of 23 gene expression changes in PC3M cells showed co-occurrence in prostate cancer patients and correlated with decreased disease-free survival.

Conclusions:

  • mHGF and NK2 can drive prostate cancer cell invasion and metastasis via the human MET receptor.
  • The HGF invasive program involves specific gene networks critical for cell motility and metastasis.
  • Identified gene expression signatures may serve as prognostic markers for prostate cancer patients.