title: Basement membrane protein ladinin-1 and the MIF-CD44-β1 integrin signaling axis are implicated in laryngeal cancer metastasis.
abstract: Laryngeal squamous cell carcinoma (LSCC) is the most common form of malignant disease in the head and neck region characterized by frequent occurrence of metastases in the neck lymph nodes early in the disease onset. In the presented study, we performed quantitative proteomic profiling of patient-matched primary tumor and adjacent non-tumorous tissues derived from metastatic LSCC as to identify new protein candidates with potential diagnostic and therapeutic significance. Obtained results revealed for the first time involvement of the basement membrane protein ladinin-1 in laryngeal cancer metastases. Alterations in the cellular microenvironment that propel metastatic events in laryngeal cancer include activation of MIF-CD44-β1 integrin signal transduction pathway and induction of downstream signaling mediated by NF-κB and Src tyrosine kinase, which ultimately impinge on cytoskeletal dynamics and architecture resulting in increased cellular motility and invasiveness. In this context, particularly interesting finding is upregulation of several actin-binding proteins novel to laryngeal cancer pathogenesis including coronin-1C and plastin-2, whose functional significance in laryngeal carcinogenesis has yet to be established. We also detected for the first time a complete loss of afamin in metastatic laryngeal cancer tissues, which warrants further studies into its use as a possible marker for monitoring disease progression and/or treatment outcome.
authors.affiliation: University of Rijeka, Department of Biotechnology, Centre for High-throughput Technologies, Radmile Matejčić 2, 51000 Rijeka, Croatia.
authors.forename: Marko
authors.initials: M
authors.lastname: Klobučar
authors.affiliation: University of Rijeka, Department of Biotechnology, Centre for High-throughput Technologies, Radmile Matejčić 2, 51000 Rijeka, Croatia.
authors.forename: Mirela
authors.initials: M
authors.lastname: Sedić
authors.affiliation: Functional Genomics Center Zürich, University of Zurich/ETH Zurich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland.
authors.forename: Peter
authors.initials: P
authors.lastname: Gehrig
authors.affiliation: Functional Genomics Center Zürich, University of Zurich/ETH Zurich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland.
authors.forename: Jonas
authors.initials: J
authors.lastname: Grossmann
authors.affiliation: University Department of ENT, Head and Neck Surgery, Kišpatićeva 12, 10000 Zagreb, Croatia.
authors.forename: Mario
authors.initials: M
authors.lastname: Bilić
authors.affiliation: University Department of ENT, Head and Neck Surgery, Kišpatićeva 12, 10000 Zagreb, Croatia.
authors.forename: Lana
authors.initials: L
authors.lastname: Kovač-Bilić
authors.affiliation: University of Rijeka, Department of Biotechnology, Centre for High-throughput Technologies, Radmile Matejčić 2, 51000 Rijeka, Croatia.
authors.forename: Krešimir
authors.initials: K
authors.lastname: Pavelić
authors.affiliation: University of Rijeka, Department of Biotechnology, Centre for High-throughput Technologies, Radmile Matejčić 2, 51000 Rijeka, Croatia. Electronic address: sandrakp@biotech.uniri.hr.
authors.forename: Sandra
authors.initials: S
authors.lastname: Kraljević Pavelić
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism*; D019012:Integrin beta1 / Q000235:genetics / Q000378:metabolism*; D019746:Intramolecular Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D007822:Laryngeal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008263:Macrophage Migration-Inhibitory Factors / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D059016:Tumor Microenvironment
chemical_list: D014408:Biomarkers, Tumor; C497483:CD44 protein, human; D018960:Hyaluronan Receptors; D019012:Integrin beta1; D008263:Macrophage Migration-Inhibitory Factors; D009363:Neoplasm Proteins; D019746:Intramolecular Oxidoreductases; C515598:MIF protein, human
keywords: Cytoskeleton; Ladinin-1; Metastases; Proteomics; Squamous larynx cancer; Src tyrosine kinase