The Crosstalk between Src and Hippo/YAP Signaling Pathways in Non-Small Cell Lung Cancer (NSCLC)
The advancement of new therapies, including targeted therapies and immunotherapies, has improved the survival of non-small-cell lung cancer (NSCLC) patients in the last decade. Some NSCLC patients still do not benefit from therapies or encounter progressive disease during the course of treatment bec...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-05-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/12/6/1361 |
| _version_ | 1797566957426311168 |
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| author | Ping-Chih Hsu Cheng-Ta Yang David M. Jablons Liang You |
| author_facet | Ping-Chih Hsu Cheng-Ta Yang David M. Jablons Liang You |
| author_sort | Ping-Chih Hsu |
| collection | DOAJ |
| description | The advancement of new therapies, including targeted therapies and immunotherapies, has improved the survival of non-small-cell lung cancer (NSCLC) patients in the last decade. Some NSCLC patients still do not benefit from therapies or encounter progressive disease during the course of treatment because they have intrinsic resistance, acquired resistance, or lack a targetable driver mutation. More investigations on the molecular biology of NSCLC are needed to find useful biomarkers for current therapies and to develop novel therapeutic strategies. Src is a non-receptor tyrosine kinase protein that interacts with cell surface growth factor receptors and the intracellular signaling pathway to maintain cell survival tumorigenesis in NSCLC. The Yes-associated protein (YAP) is one of the main effectors of the Hippo pathway and has been identified as a promoter of drug resistance, cancer progression, and metastasis in NSCLC. Here, we review studies that have investigated the activation of YAP as mediated by Src kinases and demonstrate that Src regulates YAP through three main mechanisms: (1) direct phosphorylation; (2) the activation of pathways repressing Hippo kinases; and (3) Hippo-independent mechanisms. Further work should focus on the efficacy of Src inhibitors in inhibiting YAP activity in NSCLC. In addition, future efforts toward developing potentially reasonable combinations of therapy targeting the Src–YAP axis using other therapies, including targeted therapies and/or immunotherapies, are warranted. |
| first_indexed | 2024-03-10T19:34:50Z |
| format | Article |
| id | doaj.art-87e875e1d73740289863180e783dc3e8 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T19:34:50Z |
| publishDate | 2020-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-87e875e1d73740289863180e783dc3e82023-11-20T01:49:34ZengMDPI AGCancers2072-66942020-05-01126136110.3390/cancers12061361The Crosstalk between Src and Hippo/YAP Signaling Pathways in Non-Small Cell Lung Cancer (NSCLC)Ping-Chih Hsu0Cheng-Ta Yang1David M. Jablons2Liang You3Department of Surgery, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA 94115, USADivision of Thoracic Medicine, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, College of Medicine, Chang Gung University, Taoyuan 33305, TaiwanDepartment of Surgery, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA 94115, USADepartment of Surgery, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA 94115, USAThe advancement of new therapies, including targeted therapies and immunotherapies, has improved the survival of non-small-cell lung cancer (NSCLC) patients in the last decade. Some NSCLC patients still do not benefit from therapies or encounter progressive disease during the course of treatment because they have intrinsic resistance, acquired resistance, or lack a targetable driver mutation. More investigations on the molecular biology of NSCLC are needed to find useful biomarkers for current therapies and to develop novel therapeutic strategies. Src is a non-receptor tyrosine kinase protein that interacts with cell surface growth factor receptors and the intracellular signaling pathway to maintain cell survival tumorigenesis in NSCLC. The Yes-associated protein (YAP) is one of the main effectors of the Hippo pathway and has been identified as a promoter of drug resistance, cancer progression, and metastasis in NSCLC. Here, we review studies that have investigated the activation of YAP as mediated by Src kinases and demonstrate that Src regulates YAP through three main mechanisms: (1) direct phosphorylation; (2) the activation of pathways repressing Hippo kinases; and (3) Hippo-independent mechanisms. Further work should focus on the efficacy of Src inhibitors in inhibiting YAP activity in NSCLC. In addition, future efforts toward developing potentially reasonable combinations of therapy targeting the Src–YAP axis using other therapies, including targeted therapies and/or immunotherapies, are warranted.https://www.mdpi.com/2072-6694/12/6/1361proto-oncogene tyrosine-protein kinase Srcyes-associated protein (YAP)Hippo pathwaynon-small cell lung cancer (NSCLC)tyrosine-kinase inhibitor (TKI)YES1 |
| spellingShingle | Ping-Chih Hsu Cheng-Ta Yang David M. Jablons Liang You The Crosstalk between Src and Hippo/YAP Signaling Pathways in Non-Small Cell Lung Cancer (NSCLC) Cancers proto-oncogene tyrosine-protein kinase Src yes-associated protein (YAP) Hippo pathway non-small cell lung cancer (NSCLC) tyrosine-kinase inhibitor (TKI) YES1 |
| title | The Crosstalk between Src and Hippo/YAP Signaling Pathways in Non-Small Cell Lung Cancer (NSCLC) |
| title_full | The Crosstalk between Src and Hippo/YAP Signaling Pathways in Non-Small Cell Lung Cancer (NSCLC) |
| title_fullStr | The Crosstalk between Src and Hippo/YAP Signaling Pathways in Non-Small Cell Lung Cancer (NSCLC) |
| title_full_unstemmed | The Crosstalk between Src and Hippo/YAP Signaling Pathways in Non-Small Cell Lung Cancer (NSCLC) |
| title_short | The Crosstalk between Src and Hippo/YAP Signaling Pathways in Non-Small Cell Lung Cancer (NSCLC) |
| title_sort | crosstalk between src and hippo yap signaling pathways in non small cell lung cancer nsclc |
| topic | proto-oncogene tyrosine-protein kinase Src yes-associated protein (YAP) Hippo pathway non-small cell lung cancer (NSCLC) tyrosine-kinase inhibitor (TKI) YES1 |
| url | https://www.mdpi.com/2072-6694/12/6/1361 |
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