Idioma:

The HER4-YAP1 axis promotes trastuzumab resistance in HER2-positive gastric cancer by inducing epithelial and mesenchymal transition

Shi, Jiaolong ; Li, Fengping ; Yao, Xingxing ; Mou, Tingyu ; Xu, Zhijun ; Han, Zheng ; Chen, Siyu ; Li, Wende ; Yu, Jiang ; Qi, Xiaolong ; Liu, Hao ; Li, Guoxin

Oncogene, 2018-05, Vol.37 (22), p.3022-3038 [Periódico revisado por pares]

England: Nature Publishing Group

Texto completo disponível

Citações Citado por

Enviar para

Título:
The HER4-YAP1 axis promotes trastuzumab resistance in HER2-positive gastric cancer by inducing epithelial and mesenchymal transition
Autor: Shi, Jiaolong ; Li, Fengping ; Yao, Xingxing ; Mou, Tingyu ; Xu, Zhijun ; Han, Zheng ; Chen, Siyu ; Li, Wende ; Yu, Jiang ; Qi, Xiaolong ; Liu, Hao ; Li, Guoxin
Assuntos: Adaptor Proteins, Signal Transducing - metabolism ; Animal models ; Animals ; Antigens, CD - metabolism ; Cadherins - metabolism ; Cell culture ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Cell survival ; Development and progression ; Drug resistance ; Drug Resistance, Neoplasm ; Drug therapy ; E-cadherin ; Epithelial-Mesenchymal Transition ; ErbB-2 protein ; Gastric cancer ; Gene expression ; Gene Expression Regulation, Neoplastic ; Gene silencing ; Genetic aspects ; Genetic markers ; Health aspects ; Humans ; Immunotherapy ; Mesenchyme ; Metastases ; Mice ; Monoclonal antibodies ; Neoplasm Transplantation ; Patients ; Phosphoproteins - metabolism ; Phosphorylation ; Receptor, ErbB-2 - metabolism ; Receptor, ErbB-4 - genetics ; Receptor, ErbB-4 - metabolism ; Signal Transduction ; Stomach cancer ; Stomach Neoplasms - genetics ; Stomach Neoplasms - metabolism ; Stomach Neoplasms - pathology ; Targeted cancer therapy ; Transcription Factors ; Transfection ; Trastuzumab ; Up-Regulation ; Vimentin ; Vimentin - metabolism ; Xenografts ; Yes-associated protein
É parte de: Oncogene, 2018-05, Vol.37 (22), p.3022-3038
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
Descrição: Trastuzumab is the only target to be approved as the first-line treatment of HER2 positive metastatic gastric cancer, but ubiquitous resistance decreases its therapeutic benefit. In this study, we found HER4, phosphorylation HER4 (p-HER4) and the mesenchymal marker Vimentin increased in trastuzumab-resistant cells (MKN45TR and NCI-N87TR), while epithelial markers expressions in trastuzumab-resistant cell lines and animal models decreased. Additionally, silencing HER4 prevented the epithelial-mesenchymal transition and led to decreased proliferation and migration in vitro and in vivo. The expression of YAP1, a vital downstream interacted target of HER4, decreased when HER4 was knocked down. Interestingly, stimulation of NRG1 could compromise the inhibitory impact and rescue cell survival; whereas, transfection of siYAP1 sensitized trastuzumab-treated cells. Expression analysis of the proteins in patient-derived xenograft model (PDX) mice showed that HER4, p-HER4, YAP1, and Vimentin were clearly upregulated in the trastuzumab-resistant mice compared to mice without trastuzumab resistance. However, HER2 and E-cadherin were downregulated in response to continuous treatment with trastuzumab. These findings elucidated that the central role of the HER4-YAP1 axis in trastuzumab resistance of HER2-positive gastric cancer cells through induction of EMT. Hence, regulating the HER4-YAP1 axis might be a promising strategy for clinical interventions in patients with HER2-positive gastric cancer.
Editor: England: Nature Publishing Group
Idioma: Inglês

Links

View this record in MEDLINE/PubMed

Voltar para lista de resultados

Realização: Logos de Redes Sociais:

The HER4-YAP1 axis promotes trastuzumab resistance in HER2-positive gastric cancer by inducing epithelial and mesenchymal transition

Shi, Jiaolong ; Li, Fengping ; Yao, Xingxing ; Mou, Tingyu ; Xu, Zhijun ; Han, Zheng ; Chen, Siyu ; Li, Wende ; Yu, Jiang ; Qi, Xiaolong ; Liu, Hao ; Li, Guoxin

England: Nature Publishing Group

Buscando em bases de dados remotas. Favor aguardar.