| Autor: |
Kazuki Takahashi, Katarzyna A. Podyma-Inoue, Maki Saito, Shintaro Sakakitani, Akinari Sugauchi, Keita Iida, Sadahiro Iwabuchi, Daizo Koinuma, Kyoko Kurioka, Toru Konishi, Susumu Tanaka, Atsushi Kaida, Masahiko Miura, Shinichi Hashimoto, Mariko Okada, Toshihiro Uchihashi, Kohei Miyazono, Tetsuro Watabe |
| Rok vydání: |
2022 |
| Předmět: |
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| Zdroj: |
Cell reports. 40(13) |
| ISSN: |
2211-1247 |
| Popis: |
Transforming growth factor β (TGF-β) increases epithelial cancer cell migration and metastasis by inducing epithelial-mesenchymal transition (EMT). TGF-β also inhibits cell proliferation by inducing G1 phase cell-cycle arrest. However, the correlation between these tumor-promoting and -suppressing effects remains unclear. Here, we show that TGF-β confers higher motility and metastatic ability to oral cancer cells in G1 phase. Mechanistically, keratin-associated protein 2-3 (KRTAP2-3) is a regulator of these dual effects of TGF-β, and its expression is correlated with tumor progression in patients with head and neck cancer and migratory and metastatic potentials of oral cancer cells. Furthermore, single-cell RNA sequencing reveals that TGF-β generates two populations of mesenchymal cancer cells with differential cell-cycle status through two distinctive EMT pathways mediated by Slug/HMGA2 and KRTAP2-3. Thus, TGF-β-induced KRTAP2-3 orchestrates cancer cell proliferation and migration by inducing EMT, suggesting motile cancer cells arrested in G1 phase as a target to suppress metastasis. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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