BRK phosphorylates SMAD4 for proteasomal degradation and inhibits tumor suppressor FRK to control SNAIL, SLUG, and metastatic potential

• Published in: Science advances Vol. 5; no. 10; p. eaaw3113
• Main Authors: Miah, S, Banks, C A S, Ogunbolude, Y, Bagu, E T, Berg, J M, Saraf, A, Tettey, T T, Hattem, G, Dayebgadoh, G, Kempf, C G, Sardiu, M, Napper, S, Florens, L, Lukong, K E, Washburn, M P
• Format: Journal Article
• Language: English
• Published: United States American Association for the Advancement of Science 01.10.2019
• Subjects: Biochemistry; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cell Line, Tumor; Epithelial-Mesenchymal Transition; Female; Gene Expression Regulation, Neoplastic; Genes, Tumor Suppressor; Humans; Neoplasm Proteins - genetics; Neoplasm Proteins - metabolism; Phosphorylation; Protein-Tyrosine Kinases - genetics; Protein-Tyrosine Kinases - metabolism; SciAdv r-articles; Smad4 Protein - genetics; Smad4 Protein - metabolism; Snail Family Transcription Factors - metabolism; Transforming Growth Factor beta - metabolism; Tyrosine - metabolism; Ubiquitination

The tumor-suppressing function of SMAD4 is frequently subverted during mammary tumorigenesis, leading to cancer growth, invasion, and metastasis. A long-standing concept is that SMAD4 is not regulated by phosphorylation but ubiquitination. Our search for signaling pathways regulated by breast tumor...