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HSulf-1 modulates HGF-mediated tumor cell invasion and signaling in head and neck squamous carcinoma

Oncogene volume 23, pages 1439–1447 (2004)Cite this article

Abstract

Recently, we cloned a novel sulfatase domain-containing downregulated gene, HSulf-1, which modulates heparin-binding growth factor signaling in ovarian cancer. Based on the pilot data showing the loss of HSulf-1 in head and neck squamous cell carcinoma cell lines (SCCHN), we sought to employ SCCHN as a model to define the role of HSulf-1 in the molecular regulation of tumorigenecity. Three SCCHN lines (012SCC, WMMSCC, and 015SCC) had no detectable HSulf-1 mRNA. Clonal lines of HSulf-1-expressing 012SCC attenuated the activation of ERK/mitogen-activated protein kinase (MAPK) signaling mediated by fibroblast growth factor (FGF-2) and both ERK/MAPK and Akt signaling mediated by hepatocyte growth factor (HGF). Consistent with this downregulation, phosphorylation of HGF receptor, c-Met, which is frequently overexpressed in SCCHN, was also attenuated in HSulf-1 clonal 012SCC cell lines. HGF markedly enhanced the motility and migration of vector-transfected cells in a transwell invasion chamber. However, HGF-mediated motility and invasion was attenuated in HSulf-1 clonal 012SCC cell lines. In addition, transfected cells displayed significant growth inhibition concomitant with a decrease in mitogenecity, as measured by thymidine incorporation and increased sensitivity to staurosporine- and cisplatin-induced apoptosis. These data suggest that HSulf-1 normally functions as a negative regulator in cell growth and loss of HSulf-1 in SCCHN potentiates growth factor signaling, enhances motility, invasiveness and inhibits stress-induced apoptosis, with a resulting increase in tumorigenecity.

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Acknowledgements

We thank Dr Haidong Dong for help with FACS analysis. This work was supported by Mayo Foundation (to VS) and National Institutes of Health (CA82862 to LRR), an Industry Research Scholar Award from the Foundation of Digestive Health and Nutrition (to LRR).

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Authors and Affiliations

  1. Division of Gastroenterology and Hepatology, Mayo Clinic Cancer Center, Mayo Clinic and Foundation, Rochester, 55905, MN, USA

    Jin-Ping Lai, Damian P Montoya & Lewis R Roberts

  2. Department of Otolaryngology, Xiangya Hospital, Xiang Ya School of Medicine, Central South University, Changsha, Hunan, 410008, PR, China

    Jin-Ping Lai

  3. Department of Experimental Pathology, Mayo Clinic Cancer Center, Mayo Clinic and Foundation, 200 First Street SW, Rochester, 55905, MN, USA

    Jeremy Chien, Julie Staub, David I Smith & Viji Shridhar

  4. Department of Otolaryngology-Head and Neck Surgery, Mayo Clinic Cancer Center, Mayo Clinic and Foundation, Rochester, 55905, MN, USA

    Scott E Strome

  5. Division of Nephrology, Mayo Clinic Cancer Center, Mayo Clinic and Foundation, Rochester, 55905, MN, USA

    Eddie L Greene

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  1. Jin-Ping Lai
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  2. Jeremy Chien
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  3. Scott E Strome
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  8. Lewis R Roberts
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Correspondence to Lewis R Roberts or Viji Shridhar.

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Lai, JP., Chien, J., Strome, S. et al. HSulf-1 modulates HGF-mediated tumor cell invasion and signaling in head and neck squamous carcinoma. Oncogene 23, 1439–1447 (2004). https://doi.org/10.1038/sj.onc.1207258

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