title: Loss of TACSTD2 contributed to squamous cell carcinoma progression through attenuating TAp63-dependent apoptosis.
abstract: Tumor-associated calcium signal transducer 2 (TACSTD2), a calcium signal transducer, is universally expressed in stratified squamous epithelia of many organs, including skin, esophagus and cervix. Although TACSTD2, was reported to be overexpressed in many epithelial tumors, which has increased interest in using it as a molecular target for cancer therapy, the role of TACSTD2 in carcinogenesis of squamous cell carcinoma (SCC) is largely unclear and controversial. To explore the role of TACSTD2, temporal-spatial expression of TACSTD2 was analyzed in both normal and SCC tissues. Our data demonstrate that Tacstd2 expression and membrane localization are tightly associated with stratified epithelial homeostasis, while loss of TACSTD2 was identified in poorly differentiated SCC tissues collected from cervix, esophagus, head and neck. Gradual loss of TACSTD2 was correlated with stepwise progression of SCC. Consistent with these in vivo observations, our data show that inhibition of Tacstd2 expression significantly inhibited chemotherapeutic reagent-induced apoptosis, and TACSTD2 regulated apoptotic gene expression through P63 containing the transactivation domain (TAp63). These findings indicated that loss of TACSTD2 could promote SCC progression and treatment resistance through attenuating chemotherapeutic reagent-induced apoptosis through TAp63, and TACSTD2 could be used as a marker for pathological grading of SCC.
authors.affiliation: Key Laboratory of Obstetric, Gynecologic and Pediatric Diseases and Birth Defects of the Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
authors.forename: F
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
authors.forename: X
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
authors.forename: P
authors.initials: P
authors.lastname: Yang
authors.affiliation: Department of Pathology, The First Affiliated Hospital of SooChow University, Suzhou 215006, China.
authors.forename: L
authors.initials: L
authors.lastname: Guo
authors.affiliation: Key Laboratory of Obstetric, Gynecologic and Pediatric Diseases and Birth Defects of the Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
authors.forename: C
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Anesthesiology, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
authors.forename: H
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
authors.forename: S
authors.initials: S
authors.lastname: Long
authors.affiliation: Department of Pathology, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Shen
authors.affiliation: 1] Key Laboratory of Obstetric, Gynecologic and Pediatric Diseases and Birth Defects of the Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, China [2] Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
authors.forename: H
authors.initials: H
authors.lastname: Wan
mesh_terms: D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018450:Disease Progression; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm; D004938:Esophageal Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism / Q000473:pathology; D008297:Male; D034622:RNA Interference; D015398:Signal Transduction; D000077195:Squamous Cell Carcinoma of Head and Neck; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D015815:Cell Adhesion Molecules; C499380:TACSTD2 protein, human; C115051:TP63 protein, human; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins