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Journals / Turkish Journal of Biology / 2020 / Cilt: 44 - Sayı: 4

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

Mustafa Gökhan ERTOSUN
Gamze TANRIÖVER
Sayra DİLMAÇ
Suray PEHLİVANOĞLU
Osman Nidai ÖZEŞ
Pages
158–165
Publication Date
2022-11-06
DOI
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AI Summary & Key Takeaways

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⚡ TL;DR(Too Long; Didn't Read)

Our results indicate that phosphorylation of S42 and T125 by AKT is essential for TWIST1-mediated tumor growth and metastasis.

📌 3 Key Takeaways

🎯
Objective & Hypothesis:Previously, it was shown that human TWIST1 (basic helix-loop-helix (b-HLH) is phosphorylated by Akt kinase at S42, T121, and S123.
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Key Findings & Data: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.
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Conclusion & Impact:Our results indicate that phosphorylation of S42 and T125 by AKT is essential for TWIST1-mediated tumor growth and metastasis.
🔬Design:Research Article
📍Scope:Comprehensive Sample
⚙️Variables:Domain Parameters

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 x 10(6) 67NR and 1 x 10(5) 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.

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Cite This Article

ERTOSUN, M. G., TANRIÖVER, G., DİLMAÇ, S., PEHLİVANOĞLU, S., ÖZEŞ, O. N. (2022). AKT-mediated phosphorylation of TWIST1 is essential for breast cancer cell metastasis. Turkish Journal of Biology, Cilt: 44 - Sayı: 4, 158–165. https://ajindex.com/articles/654387

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