RRC ID 72687
著者 Takahashi K, Podyma-Inoue KA, Saito M, Sakakitani S, Sugauchi A, Iida K, Iwabuchi S, Koinuma D, Kurioka K, Konishi T, Tanaka S, Kaida A, Miura M, Hashimoto S, Okada M, Uchihashi T, Miyazono K, Watabe T.
タイトル TGF-β generates a population of cancer cells residing in G1 phase with high motility and metastatic potential via KRTAP2-3.
ジャーナル Cell Rep
Abstract 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.
巻・号 40(13)
ページ 111411
公開日 2022-9-27
DOI 10.1016/j.celrep.2022.111411
PII S2211-1247(22)01252-9
PMID 36170816
MeSH Cell Line, Tumor Cell Movement Epithelial-Mesenchymal Transition / genetics G1 Phase Cell Cycle Checkpoints Gene Expression Regulation, Neoplastic Humans Keratins / metabolism Mouth Neoplasms* / genetics Transforming Growth Factor beta* / metabolism Transforming Growth Factor beta1 / metabolism
IF 8.109
リソース情報
ヒト・動物細胞 SAS(RCB1974) HSC-4(RCB1902)