title: Yes-Associated Protein Contributes to the Development of Human Cutaneous Squamous Cell Carcinoma via Activation of RAS.
abstract: Cutaneous squamous cell carcinoma (cSCC) is one of the most common skin malignant tumors with an increasing incidence. Studies have shown that Yes-associated protein (YAP) participates in the development of a variety of tumors as an oncogene, but to our knowledge its role in cSCC has not been reported. In this study, we used immunohistochemistry to show that YAP expression was elevated in cSCC samples of different stages versus in normal skin and that it was well correlated with the progression of the disease. Down-regulation of YAP in cSCC cell lines A431 and SCL-1 inhibited cell proliferation by inducing growth arrest during the G1/S phase transition, promoted apoptosis, and reduced invasion and migration abilities in vitro. Conversely, overexpression of YAP promoted cell proliferation and protected cells against basal and chemotherapy-induced apoptosis. These oncogenic effects of YAP were associated with activation of the RAS protein and its downstream AKT and ERK. Using a mouse xenograft model, we further showed that YAP depletion inhibited cSCC tumor growth in vivo. Our results suggested that YAP is involved in the carcinogenesis and development of cSCC and that it may serve as a biomarker or therapeutic target of this disease.
authors.affiliation: Department of Dermatology, the Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, China.
authors.forename: Jinjing
authors.initials: J
authors.lastname: Jia
authors.affiliation: Department of Dermatology, the Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, China.
authors.forename: Changji
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Dermatology, Tianjin Medical University General Hospital, Tianjin, China.
authors.forename: Suju
authors.initials: S
authors.lastname: Luo
authors.affiliation: Departments of Epidemiology and Medicine, University of California Irvine, Irvine, CA, USA.
authors.forename: Feng
authors.initials: F
authors.lastname: Liu-Smith
authors.affiliation: Department of Dermatology, the Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, China.
authors.forename: Jiao
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Dermatology, the Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Cardiovascular Research Center, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, China.
authors.forename: Nanping
authors.initials: N
authors.lastname: Wang
authors.affiliation: Cardiovascular Research Center, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, China.
authors.forename: Baochang
authors.initials: B
authors.lastname: Lai
authors.affiliation: Cardiovascular Research Center, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, China; Department of Pathology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Lei
authors.affiliation: Department of Dermatology, the Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, China.
authors.forename: Qiongyu
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Dermatology, the Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, China.
authors.forename: Shengxiang
authors.initials: S
authors.lastname: Xiao
authors.affiliation: Key Laboratory of Biomedical Information Engineering of the Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, China; Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, China. Electronic address: yongpings@gmail.com.
authors.forename: Yongping
authors.initials: Y
authors.lastname: Shao
authors.affiliation: Department of Dermatology, the Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, China. Electronic address: zenyan66@126.com.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zheng
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D002478:Cells, Cultured; D004195:Disease Models, Animal; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015603:Keratinocytes / Q000166:cytology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D051575:Proto-Oncogene Proteins c-yes / Q000235:genetics*; D034741:RNA, Small Interfering / Q000378:metabolism; D012494:Sampling Studies; D015398:Signal Transduction; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology; D018631:ras Proteins / Q000378:metabolism*
chemical_list: D034741:RNA, Small Interfering; D051575:Proto-Oncogene Proteins c-yes; C489834:YES1 protein, human; D018631:ras Proteins