Yes-associated protein regulates the growth of human non-small cell lung cancer in response to matrix stiffness

Yuan,Yonggang; Zhong,Weiliang; Ma,Ge; Zhang,Baoxiang; Tian,Hui

doi:10.3892/mmr.2015.3231

June-2015 Volume 11 Issue 6

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June-2015 Volume 11 Issue 6

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Article

Yes-associated protein regulates the growth of human non-small cell lung cancer in response to matrix stiffness

Authors:
- Yonggang Yuan
- Weiliang Zhong
- Ge Ma
- Baoxiang Zhang
- Hui Tian
View Affiliations / Copyright

Affiliations: Department of Thoracic Surgery, Qi Lu Hospital, Shandong Medical University, Jinan, Shandong 250100, P.R. China, Department of Orthopedics, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China, Department of Thoracic Surgery, Yidu Central Hospital, Weifang Medical University, Weifang, Shandong 262500, P.R. China, Department of Dermatology, Yidu Central Hospital, Weifang Medical University, Weifang, Shandong 262500, P.R. China
Pages: 4267-4272
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Published online on: January 20, 2015

https://doi.org/10.3892/mmr.2015.3231
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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.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Yes-associated protein regulates the growth of human non-small cell lung cancer in response to matrix stiffness

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