Unknown

Dataset Information

0

Treatment-Induced Tumor Dormancy through YAP-Mediated Transcriptional Reprogramming of the Apoptotic Pathway.

ABSTRACT: Eradicating tumor dormancy that develops following epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) treatment of EGFR-mutant non-small cell lung cancer, is an attractive therapeutic strategy but the mechanisms governing this process are poorly understood. Blockade of ERK1/2 reactivation following EGFR TKI treatment by combined EGFR/MEK inhibition uncovers cells that survive by entering a senescence-like dormant state characterized by high YAP/TEAD activity. YAP/TEAD engage the epithelial-to-mesenchymal transition transcription factor SLUG to directly repress pro-apoptotic BMF, limiting drug-induced apoptosis. Pharmacological co-inhibition of YAP and TEAD, or genetic deletion of YAP1, all deplete dormant cells by enhancing EGFR/MEK inhibition-induced apoptosis. Enhancing the initial efficacy of targeted therapies could ultimately lead to prolonged treatment responses in cancer patients.

SUBMITTER: Kurppa KJ 

PROVIDER: S-EPMC7146079 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

Json Xml
altmetric image

Publications

Treatment-Induced Tumor Dormancy through YAP-Mediated Transcriptional Reprogramming of the Apoptotic Pathway.

Kurppa Kari J KJ   Liu Yao Y   To Ciric C   Zhang Tinghu T   Fan Mengyang M   Vajdi Amir A   Knelson Erik H EH   Xie Yingtian Y   Lim Klothilda K   Cejas Paloma P   Portell Andrew A   Lizotte Patrick H PH   Ficarro Scott B SB   Li Shuai S   Chen Ting T   Chen Ting T   Haikala Heidi M HM   Wang Haiyun H   Bahcall Magda M   Gao Yang Y   Shalhout Sophia S   Boettcher Steffen S   Shin Bo Hee BH   Thai Tran T   Wilkens Margaret K MK   Tillgren Michelle L ML   Mushajiang Mierzhati M   Xu Man M   Choi Jihyun J   Bertram Arrien A AA   Ebert Benjamin L BL   Beroukhim Rameen R   Bandopadhayay Pratiti P   Awad Mark M MM   Gokhale Prafulla C PC   Kirschmeier Paul T PT   Marto Jarrod A JA   Camargo Fernando D FD   Haq Rizwan R   Paweletz Cloud P CP   Wong Kwok-Kin KK   Barbie David A DA   Long Henry W HW   Gray Nathanael S NS   Jänne Pasi A PA  

Cancer cell 20200101 1

Eradicating tumor dormancy that develops following epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) treatment of EGFR-mutant non-small cell lung cancer, is an attractive therapeutic strategy but the mechanisms governing this process are poorly understood. Blockade of ERK1/2 reactivation following EGFR TKI treatment by combined EGFR/MEK inhibition uncovers cells that survive by entering a senescence-like dormant state characterized by high YAP/TEAD activity. YAP/TEAD engage  ...[more]

Similar Datasets

Transcriptomics Treatment-induced tumor dormancy through YAP-mediated transcriptional reprogramming of the apoptotic pathway
2020-01-13 | GSE131604 | GEO
Transcriptomics Treatment-induced tumor dormancy through YAP-mediated transcriptional reprogramming of the apoptotic pathway [scRNASeq]
2020-01-13 | GSE138693 | GEO
Genomics Treatment-induced tumor dormancy through YAP-mediated transcriptional reprogramming of the apoptotic pathway [ChIP + ATAC]
2020-01-13 | GSE131687 | GEO
Transcriptomics Treatment-induced tumor dormancy through YAP-mediated transcriptional reprogramming of the apoptotic pathway [DMSO vs DORMANT]
2020-01-13 | GSE131594 | GEO
Transcriptomics Treatment-induced tumor dormancy through YAP-mediated transcriptional reprogramming of the apoptotic pathway [YAP1 KO vs CTRL]
2020-01-13 | GSE131601 | GEO
Genomics Treatment-induced tumor dormancy through YAP-mediated transcriptional reprogramming of the apoptotic pathway
| PRJNA544121 | ENA
Genomics Treatment-induced tumor dormancy through YAP-mediated transcriptional reprogramming of the apoptotic pathway [scRNASeq]
| PRJNA576817 | ENA
Genomics Treatment-induced tumor dormancy through YAP-mediated transcriptional reprogramming of the apoptotic pathway [ChIP + ATAC]
| PRJNA544436 | ENA
Genomics Treatment-induced tumor dormancy through YAP-mediated transcriptional reprogramming of the apoptotic pathway [DMSO vs DORMANT]
| PRJNA544106 | ENA
Genomics Treatment-induced tumor dormancy through YAP-mediated transcriptional reprogramming of the apoptotic pathway [YAP1 KO vs CTRL]
| PRJNA544119 | ENA