title: Anterior gradient protein 2 expression in high grade head and neck squamous cell carcinoma correlated with cancer stem cell and epithelial mesenchymal transition.
abstract: Anterior gradient protein 2 (AGR2) is a novel biomarker with potential oncogenic role. We sought to investigate the diagnostic and prognostic role of AGR2 on head and neck squamous cell carcinoma (HNSCC) with an emphasis on its correlation of cancer stemloid cells (CSC) and epithelial mesenchymal transition (EMT). We found that AGR2 protein levels were higher in HNSCC than in normal oral mucosa. High levels of AGR2 were associated with the T category, pathological grade and lymph node metastasis of HNSCC. Expression of AGR2 increased in recurring HNSCC after radiotherapy and in post cisplatin-based chemotherapeutic tissues. In HNSCC cell lines, knock-down of AGR2 induced apoptosis, reduced sphere formation, and down-regulated Survivin, Cyclin D1, Bcl2, Bcl2l1, Slug, Snail, Nanog and Oct4. In addition, over-expressed AGR2 in transgenic mice with spontaneous HNSCC was associated with lost function of Tgfbr1 and/ or lost function of Pten. In vitro knockdown TGFBR1 in HNSCC cell lines increased AGR2 expression. These results suggest that AGR2 is involved in EMT and self-renewal of CSC and may present a potential therapeutic target (oncotarget) for HNSCC.
authors: The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine Ministry of Education, Wuhan University, Wuhan, China.
authors: Si-Rui
authors: SR
authors: Ma
authors: The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine Ministry of Education, Wuhan University, Wuhan, China.
authors: Wei-Ming
authors: WM
authors: Wang
authors: The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine Ministry of Education, Wuhan University, Wuhan, China.
authors: Cong-Fa
authors: CF
authors: Huang
authors: The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine Ministry of Education, Wuhan University, Wuhan, China.|Department of Oral Maxillofacial-Head Neck Oncology, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
authors: Wen-Feng
authors: WF
authors: Zhang
authors: The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine Ministry of Education, Wuhan University, Wuhan, China.|Department of Oral Maxillofacial-Head Neck Oncology, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
authors: Zhi-Jun
authors: ZJ
authors: Sun
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D045744:Cell Line, Tumor; D000066673:Cell Self Renewal / Q000235:genetics; D002945:Cisplatin / Q000008:administration & dosage / Q000494:pharmacology; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005472:Fluorouracil / Q000008:administration & dosage / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000528:radiation effects; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D006801:Humans; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D018345:Mice, Knockout; D009061:Mouth Mucosa / Q000737:chemistry; D009088:Mucoproteins; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D015513:Oncogene Proteins; D051059:PTEN Phosphohydrolase / Q000172:deficiency / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency / Q000235:genetics; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D034741:RNA, Small Interfering; D018714:Radiotherapy, Adjuvant; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000172:deficiency / Q000235:genetics; D018874:Spheroids, Cellular; D043823:Taxoids / Q000008:administration & dosage / Q000494:pharmacology; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics
chemical_list: C502296:AGR2 protein, human; D051017:Apoptosis Regulatory Proteins; D009088:Mucoproteins; D009363:Neoplasm Proteins; D015513:Oncogene Proteins; D011506:Proteins; D034741:RNA, Small Interfering; D018125:Receptors, Transforming Growth Factor beta; D043823:Taxoids; D014157:Transcription Factors; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; C000625841:TGFBR1 protein, human; C000625842:Tgfbr1 protein, mouse; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; C487757:Pten protein, mouse; D002945:Cisplatin; D005472:Fluorouracil
keywords: AGR2; HNSCC; cancer stemloid cell; epithelial mesenchymal transition