title: Yes-associated protein regulates the growth of human non-small cell lung cancer in response to matrix stiffness.
abstract: The Yes‑associated protein (YAP) transcriptional coactivator is recognized as a crucial regulator of human cancer. However, its involvement in human non‑small cell lung cancer (NSCLC) in response to physical cues remains unclear. In this study, substrates with different rigidity were generated in order to evaluate the role of YAP, and its upstream regulators in the Hippo pathway, in the regulation of growth of an NSCLC cell line within particular environments. It was shown that the expression of the YAP protein in SPCA-1 NSCLC cells was significantly increased when cultured on a stiff substrate compared to a soft substrate. However, the expression of phospho‑YAP protein and large tumor suppressor kinase 1 (LATS1) were markedly decreased after culturing on the stiff substrate. Phosphorylation of YAP by LATS1 leads to cytoplasmic retention of YAP, which inhibits its function as a nuclear transcription coactivator. The study also found that the stiff substrate promoted the growth of NSCLC cells in vitro, and an increase in the transcription levels of Survivin, connective tissue growth factor, amphiregulin and Ki67, as well as a decrease in the expression level of YAP in the cytoplasm, and adecrease in p-YAP. In conclusion, the findings showed that the stiffness of the subcellular matrix altered the behavior of NSCLC cells, and that YAP regulated the growth of NSCLC cells in response to matrix stiffness, thereby suggesting a role for the Hippo‑YAP pathway in the response of NSCLC cell growth to specific microenvironments.
authors.affiliation: Department of Thoracic Surgery, Qi Lu Hospital, Shandong Medical University, Jinan, Shandong 250100, P.R. China.
authors.forename: Yonggang
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Department of Orthopedics, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China.
authors.forename: Weiliang
authors.initials: W
authors.lastname: Zhong
authors.affiliation: Department of Thoracic Surgery, Yidu Central Hospital, Weifang Medical University, Weifang, Shandong 262500, P.R. China.
authors.forename: Ge
authors.initials: G
authors.lastname: Ma
authors.affiliation: Department of Dermatology, Yidu Central Hospital, Weifang Medical University, Weifang, Shandong 262500, P.R. China.
authors.forename: Baoxiang
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Thoracic Surgery, Qi Lu Hospital, Shandong Medical University, Jinan, Shandong 250100, P.R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Tian
mesh_terms: D066258:Amphiregulin; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D018797:Cell Cycle Proteins; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D055513:Connective Tissue Growth Factor / Q000235:genetics / Q000378:metabolism; D066255:EGF Family of Proteins / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism; D019394:Ki-67 Antigen / Q000235:genetics / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport; D000077022:Survivin; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: C587848:AREG protein, human; D066258:Amphiregulin; C107489:BIRC5 protein, human; C526317:CCN2 protein, human; D018797:Cell Cycle Proteins; D066255:EGF Family of Proteins; D051034:Inhibitor of Apoptosis Proteins; D019394:Ki-67 Antigen; D009687:Nuclear Proteins; D000077022:Survivin; D014157:Transcription Factors; C456659:YY1AP1 protein, human; D055513:Connective Tissue Growth Factor; C092745:LATS1 protein, human; D017346:Protein Serine-Threonine Kinases