title: Hypoxia induces TFE3 expression in head and neck squamous cell carcinoma.
abstract: To assess the role of transcription factor μE3 (TFE3) in the tumorigenesis of head and neck squamous cell carcinoma (HNSCC), human HNSCC tissue arrays were investigated for TFE3 expression. Human HNSCC tissues with neoadjuvant inductive chemotherapey (docetaxel, cisplatin and fluorouracil, TPF) and mice HNSCC tissues from transgenic mice model were evaluated for TFE3 expression and the hypoxia pathway. The roles of EGF/EGFR mediated hypoxia in TFE3 nuclear expression were analyzed in vitro and in vivo. TFE3 expression was higher in human HNSCC tissues compared with that in normal oral mucosa. Moreover, high TFE3 expression was related to HIF-1α, PAI-1, and EGFR, which demonstrated the activation of the hypoxia pathway in HNSCC tissues. Furthermore, elevated TFE3 expression was observed in HNSCC after cisplatin-based chemotherapy, and high TFE3 expression may indicate poor response to TPF inductive chemotherapy. Furthermore, similar changes with increased TFE3 were observed in HNSCC of the transgenic mouse HNSCC model. Hypoxic culture in the human HNSCC cell line increased TFE3 expression, which promoted cell survival under hypoxia. EGFR inhibiton by cetuximab could attenuate hypoxia-induced TFE3 in the HNSCC cell line and transgenic mouse HNSCC model. These findings indicated that TFE3 was an important hypoxia-induced transcriptional factor in HNSCC. TFE3 could be regarded as a durgable therapeutic oncotarget by EGFR inhibition.
authors.affiliation: The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine Ministry of Education, Wuhan, China.|Department of Oral Maxillofacial-Head Neck Oncology, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
authors.forename: Zhi-Jun
authors.initials: ZJ
authors.lastname: Sun
authors.affiliation: The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine Ministry of Education, Wuhan, China.
authors.forename: Guang-Tao
authors.initials: GT
authors.lastname: Yu
authors.affiliation: The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine Ministry of Education, Wuhan, China.
authors.forename: Cong-Fa
authors.initials: CF
authors.lastname: Huang
authors.affiliation: The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine Ministry of Education, Wuhan, China.
authors.forename: Lin-Lin
authors.initials: LL
authors.lastname: Bu
authors.affiliation: The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine Ministry of Education, Wuhan, China.
authors.forename: Jian-Feng
authors.initials: JF
authors.lastname: Liu
authors.affiliation: The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine Ministry of Education, Wuhan, China.
authors.forename: Si-Rui
authors.initials: SR
authors.lastname: Ma
authors.affiliation: The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine Ministry of Education, Wuhan, China.|Department of Oral Maxillofacial-Head Neck Oncology, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
authors.forename: Wen-Feng
authors.initials: WF
authors.lastname: Zhang
authors.affiliation: The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine Ministry of Education, Wuhan, China.|Department of Oral Maxillofacial-Head Neck Oncology, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Liu
authors.affiliation: The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine Ministry of Education, Wuhan, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015687:Cell Hypoxia / Q000187:drug effects / Q000502:physiology*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D066246:ErbB Receptors / Q000378:metabolism; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D058258:Serpin E2 / Q000378:metabolism; D000077195:Squamous Cell Carcinoma of Head and Neck; D014162:Transfection
chemical_list: D000970:Antineoplastic Agents; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; C497442:HIF1A protein, human; C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human; D058258:Serpin E2; C511869:Serpine2 protein, mouse; C069203:TFE3 protein, human; C068486:Tcfe3 protein, mouse; C512478:EGFR protein, human; C541485:EGFR protein, mouse; D066246:ErbB Receptors; D002945:Cisplatin
keywords: TFE3; chemotherapy; head and neck cancer; hypoxia