AKT-mediated phosphorylation of TWIST1 is essential for breast cancer cell metastasis.

Content Provider	Europe PMC
Author	ERTOSUN, Mustafa Gökhan PEHLİVANOĞLU, Suray DİLMAÇ, Sayra TANRIÖVER, Gamze ÖZEŞ, Osman Nidai
Copyright Year	2020
Abstract	Previously, it was shown that human TWIST1 (basic helix-loop-helix (b-HLH) is phosphorylated by Akt kinase at S42, T121, and S123. To show in vivo effect of these phosphorylations, we created mouse TWIST1 expression vector and converted the codons of S42, T125, and S127 to unphosphorylatable alanine and phosphorylation mimicking Glutamic acid. We hypothesized that alanine mutants would inhibit the metastatic ability of 4T1 cells while glutamic acid mutants would convert nonmetastatic 67NR cells into metastatic phenotype. To confirm this hypothesis, we created metastatic 4T1 and nonmetastatic 67NR cells expressing alanine mutants and glutamic acid mutants mouse TWIST1, respectively. Then, we injected 1 × 106 67NR and 1 × 105 4T1 cells overexpressing mutants of TWIST1 into the breast tissue of BALB/c mice. At the end of the 4th week, we sacrificed the animals, determined the numbers of tumors at lungs and liver. Although 67NR cells overexpressing wild-type TWIST1 did not show any metastasis, cells overexpressing S42E and T125E mutants showed 15–30 macroscopic metastasis to liver and lungs. Parallel to this, 4T1 cells expressing S42A and T125A mutants of TWIST1 showed no macroscopic metastasis. Our results indicate that phosphorylation of S42 and T125 by AKT is essential for TWIST1-mediated tumor growth and metastasis.
Related Links	https://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC7478131&blobtype=pdf
ISSN	13000152
Journal	Turkish Journal of Biology [Turk J Biol]
Volume Number	44
DOI	10.3906/biy-1912-74
PubMed Central reference number	PMC7478131
Issue Number	4
PubMed reference number	32922123
e-ISSN	13036092
Language	English
Publisher	The Scientific and Technological Research Council of Turkey
Publisher Date	2020-08-19
Access Restriction	Open
Rights License	This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use and redistribution provided that the original author and source are credited. Copyright © 2020 The Author(s)
Subject Keyword	TWIST1 breast cancer metastasis
Content Type	Text
Resource Type	Article
Subject	Cell Biology Genetics Physiology Molecular Biology Microbiology Agricultural and Biological Sciences