ALK phosphorylates SMAD4 on tyrosine to disable TGF-β tumour suppressor functions

• Published in: Nature cell biology Vol. 21; no. 2; pp. 179 - 189
• Main Authors: Zhang, Qianting, Xiao, Mu, Gu, Shuchen, Xu, Yongxian, Liu, Ting, Li, Hao, Yu, Yi, Qin, Lan, Zhu, Yezhang, Chen, Fenfang, Wang, Yulong, Ding, Chen, Wu, Hongxing, Ji, Hongbin, Chen, Zhe, Zu, Youli, Malkoski, Stephen, Li, Yi, Liang, Tingbo, Ji, Junfang, Qin, Jun, Xu, Pinglong, Zhao, Bin, Shen, Li, Lin, Xia, Feng, Xin-Hua
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.02.2019; Nature Publishing Group
• Subjects: 631/67; 631/80/458/1733; 631/80/86; Anaplastic Lymphoma Kinase - genetics; Anaplastic Lymphoma Kinase - metabolism; Animals; Biomedical and Life Sciences; Blocking; Cancer; Cancer Research; Cell Biology; Cell Line; Cell Line, Tumor; Deoxyribonucleic acid; Developmental Biology; DNA; Gene Expression Profiling - methods; Gene Expression Regulation, Neoplastic - drug effects; HEK293 Cells; Humans; Kinases; Life Sciences; Lung cancer; Lymphoma; Mice, Inbred BALB C; Mice, Nude; Mutation; Neoplasms - genetics; Neoplasms - metabolism; Neoplasms - pathology; Neuroblastoma; Organic chemistry; Pancreatic cancer; Phosphorylation; Protein-tyrosine kinase; Signal transduction; Smad4 protein; Smad4 Protein - genetics; Smad4 Protein - metabolism; Stem Cells; Transduction; Transforming Growth Factor beta - pharmacology; Transplantation, Heterologous; Tumor suppressor genes; Tumorigenesis; Tumors; Tyrosine; Tyrosine - genetics; Tyrosine - metabolism

Loss of TGF-β tumour suppressive response is a hallmark of human cancers. As a central player in TGF-β signal transduction, SMAD4 (also known as DPC4) is frequently mutated or deleted in gastrointestinal and pancreatic cancer. However, such genetic alterations are rare in most cancer types and the u...