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大学・研究所にある論文を検索できる 「JNK and Yorkie drive tumor malignancy by inducing L-amino acid transporter 1 in Drosophila」の論文概要。リケラボ論文検索は、全国の大学リポジトリにある学位論文・教授論文を一括検索できる論文検索サービスです。
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JNK and Yorkie drive tumor malignancy by inducing L-amino acid transporter 1 in Drosophila

Cong, Bojie Nakamura, Mai Sando, Yukari Kondo, Takefumi Ohsawa, Shizue Igaki, Tatsushi 京都大学 DOI:10.1371/journal.pgen.1009893

2021.11

概要

Identifying a common oncogenesis pathway among tumors with different oncogenic muta-tions is critical for developing anti-cancer strategies. Here, we performed transcriptome analyses on two different models of Drosophila malignant tumors caused by Ras activation with cell polarity defects (RasV12/scrib-/-) or by microRNA bantam overexpression with endo- cytic defects (bantam/rab5-/-), followed by an RNAi screen for genes commonly essential for tumor growth and malignancy. We identified that Juvenile hormone Inducible-21 (JhI-21), a Drosophila homolog of the L-amino acid transporter 1 (LAT1), is upregulated in these malig- nant tumors with different oncogenic mutations and knocking down of JhI-21 strongly blocked their growth and invasion. JhI-21 expression was induced by simultaneous activa- tion of c-Jun N-terminal kinase (JNK) and Yorkie (Yki) in these tumors and thereby contrib- uted to tumor growth and progression by activating the mTOR-S6 pathway.

Pharmacological inhibition of LAT1 activity in Drosophila larvae significantly suppressed growth of RasV12/scrib-/- tumors. Intriguingly, LAT1 inhibitory drugs did not suppress growth of bantam/rab5-/- tumors and overexpression of bantam rendered RasV12/scrib-/- tumors unresponsive to LAT1 inhibitors. Further analyses with RNA sequencing of bantam- expressing clones followed by an RNAi screen suggested that bantam induces drug resis- tance against LAT1 inhibitors via downregulation of the TMEM135-like gene CG31157. Our observations unveil an evolutionarily conserved role of LAT1 induction in driving Drosophila tumor malignancy and provide a powerful genetic model for studying cancer progression and drug resistance.

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