論文 - 詳細
| RRC ID | 58827 |
|---|---|
| 著者 | Yamazaki S, Su Y, Maruyama A, Makinoshima H, Suzuki J, Tsuboi M, Goto K, Ochiai A, Ishii G. |
| タイトル | Uptake of collagen type I via macropinocytosis cause mTOR activation and anti-cancer drug resistance. |
| ジャーナル | Biochem Biophys Res Commun |
| Abstract |
Collagen type I (Col I) is one of the major extracellular matrix proteins in the cancer tissue. Previously, we have reported that Col I induces epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) resistance by mTOR activation through Akt and ERK1/2 independent pathway. In this study, we aimed to elucidate the molecular mechanism of Col I induced EGFR-TKI resistance. First, we demonstrated the uptake of fluorescently labeled Col I by EGFR-mutated lung cancer cell line PC-9 cells using confocal microscopy and flow cytometry. Metabolome analysis revealed that the metabolic profiles of PC-9 cells was influenced by Col I treatment. Uptake of Col I into PC-9 cells was not inhibited by MMP inhibitor, GM6001, and endocytosis inhibitors, Pitstop2 and Dyngo4a; however, macropinocytosis inhibitor EIPA prevented its uptake. Moreover, the combination of EIPA and EGFR-TKI abrogated Col I-induced EGFR-TKI resistance in PC-9 cells. Inhibition of Rac1, which is essential for micropinocytosis, also decreased the uptake of Col I in PC-9 cells and restored their sensitivity to EGFR-TKI. Thus, EGFR mutated lung cancer cells could develop EGFR-TKI resistance by Col I uptake by macropinocytosis route. |
| 巻・号 | 526(1) |
| ページ | 191-198 |
| 公開日 | 2020-5-21 |
| DOI | 10.1016/j.bbrc.2020.03.067 |
| PII | S0006-291X(20)30552-0 |
| PMID | 32201076 |
| MeSH | Amino Acids / metabolism Antineoplastic Agents / pharmacology* Cell Line, Tumor Collagen Type I / metabolism* Cytoplasm / drug effects Cytoplasm / metabolism Drug Resistance, Neoplasm* / drug effects ErbB Receptors / metabolism Gefitinib / pharmacology Humans Mechanistic Target of Rapamycin Complex 1 / metabolism Metabolomics Pinocytosis* / drug effects Protein Kinase Inhibitors / pharmacology TOR Serine-Threonine Kinases / metabolism* rac1 GTP-Binding Protein / metabolism |
| IF | 2.985 |
| 引用数 | 0 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 2 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | TE-10(RCB2099) |