title: Clinical and molecular implications of MED15 in head and neck squamous cell carcinoma.
abstract: Head and neck squamous cell carcinoma (HNSCC) progression depends on various dysregulated pathways. Regulation of diverse pathways is mediated by the mediator complex. The mediator subunit MED15 is essential for transforming growth factor (TGF)-β signaling and involved in breast and prostate cancers. We investigated the implication of MED15 in HNSCC. IHC for MED15 was performed on 324 tissue samples, and TGF-β assessed the use of Ki-67 and pSMAD3 as markers. MED15 knockdown followed by proliferation and migration assays, as well as TGF-β1 treatment followed by MED15 analysis, was also performed. MED15 was overexpressed in 35% of primary tumors, 30% of lymph node metastases, and 70% of recurrences in contrast to no or low expression in benign tumors. MED15 overexpression in primary tumors from patients who developed recurrences was associated with higher mortality rates and occurred at highest frequency in oral cavity or oropharyngeal tumors. Furthermore, MED15 expression correlated between primary tumors and corresponding lymph node metastases. MED15 correlated with proliferation in tissues, and MED15 knockdown reduced proliferation and migration. We observed an association between MED15 and TGF-β activity in tissues because TGF-β activation led to increased MED15 expression and reduced pSMAD3 on MED15 knockdown. Taken together, our results implicate MED15 in HNSCC and hint that MED15 overexpression is a clonal event during HNSCC progression. MED15 may serve as a prognostic marker for recurrence and as a therapeutic target.
authors: Department of Prostate Cancer Research, University Hospital of Bonn, Bonn, Germany; Institute of Pathology, University Hospital of Bonn, Bonn, Germany.
authors: David
authors: D
authors: Adler
authors: Department of Prostate Cancer Research, University Hospital of Bonn, Bonn, Germany; Institute of Pathology, University Hospital of Bonn, Bonn, Germany.
authors: Anne
authors: A
authors: Offermann
authors: Department of Prostate Cancer Research, University Hospital of Bonn, Bonn, Germany; Institute of Pathology, University Hospital of Bonn, Bonn, Germany.
authors: Rebecca
authors: R
authors: Halbach
authors: Department of Prostate Cancer Research, University Hospital of Bonn, Bonn, Germany; Institute of Pathology, University Hospital of Bonn, Bonn, Germany.
authors: Wenzel
authors: W
authors: Vogel
authors: Department of Prostate Cancer Research, University Hospital of Bonn, Bonn, Germany; Institute of Pathology, University Hospital of Bonn, Bonn, Germany.
authors: Martin
authors: M
authors: Braun
authors: Institute of Pathology, University Hospital of Bonn, Bonn, Germany.
authors: Glen
authors: G
authors: Kristiansen
authors: Department of Otorhinolaryngology, University Hospital of Bonn, Bonn, Germany.
authors: Friedrich
authors: F
authors: Bootz
authors: Department of Experimental Dermatology, University Hospital of Bonn, Bonn, Germany.
authors: Jörg
authors: J
authors: Wenzel
authors: Karlsruhe Institute of Technology, Institute for Applied Computer Science, Karlsruhe, Germany.
authors: Ralf
authors: R
authors: Mikut
authors: Department of Biomedicine, University Hospital Basel, Basel, Switzerland.
authors: Claudia
authors: C
authors: Lengerke
authors: Karlsruhe Institute of Technology, Institute for Applied Computer Science, Karlsruhe, Germany.
authors: Markus
authors: M
authors: Reischl
authors: Department of Otorhinolaryngology, University Hospital of Bonn, Bonn, Germany.
authors: Andreas
authors: A
authors: Schröck
authors: Department of Prostate Cancer Research, University Hospital of Bonn, Bonn, Germany; Institute of Pathology, University Hospital of Bonn, Bonn, Germany. Electronic address: sven.perner1972@gmail.com.
authors: Sven
authors: S
authors: Perner
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002999:Clone Cells; D018450:Disease Progression; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D006801:Humans; D008207:Lymphatic Metastasis / Q000473:pathology; D056892:Mediator Complex / Q000378:metabolism*; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: C416944:MED15 protein, human; D056892:Mediator Complex; D016212:Transforming Growth Factor beta