ニューロンは,臓がんにおけるmRNA翻訳をサポートするためにセリンを放出する
Robert S Banh1, Douglas E Biancur1, Keisuke Yamamoto1
1Department of Radiation Oncology, Perlmutter Cancer Center, New York University Medical Center, New York, NY 10016, USA.
Cell
|November 3, 2020
まとめ
周辺アクソンは 臓がん細胞にセリンを供給し 栄養不足の環境で腫瘍の成長を促します 神経成長因子を阻害することで,臓管腺がんの進行をさらに抑制します.
科学分野:
- 腫瘍学
- 神経科学
- メタボリズム
背景:
- 管腺がん (PDAC) 腫瘍は,栄養が乏しく,デスマプラスティックで,神経化された微小環境で存在します.
- 神経細胞はPDACを促進する因子を放出しますが,周辺軸索の代謝的役割は未知のままです.
研究 の 目的:
- PDACの成長に対する周辺軸索の代謝的貢献を調査する.
- 栄養素欠乏に対するPDAC細胞の適応と軸索セリン放出の相互作用を調査する.
主な方法:
- 周辺アクソンからのセリン (Ser) の放出を評価する.
- セル/グリ欠乏下でPDAC細胞の成長を研究した.
- Ser コドンと神経成長因子 (NGF) の分泌を分析した.
- Ser/Glyフリーダイエット中のPDAC腫瘍のマウスモデルを使用した.
- Trk-NGF阻害剤であるLOXO-101を投与し,神経内置を阻害した.
主要な成果:
- 周辺軸索はセルリンを放出し,セル/グリ欠乏時に外因的なセル (exSer) に依存するPDAC細胞をサポートする.
- セリン欠乏は,特定のセールコドン (TCC,TCT) のリボソーム停滞を引き起こし,選択的なNGF翻訳とPDAC細胞による分泌を促進した.
- PDAC腫瘍は,セル/グライフリーダイエットを受けたマウスの内置が強化され,成長が遅くなりました.
- NGFシグナル伝達をLOXO-101で抑制すると,PDAC腫瘍の成長がさらに減少した.
結論:
- PDACの適応と栄養不足の条件での成長には,アクソナル癌の代謝交響が不可欠である.
- 軸索からのセリン供給とNGF媒介の内置は,このクロストークの重要な構成要素です.
- NGFシグナリングをターゲットにすることは,PDACの潜在的な治療戦略です.
関連する概念動画
MicroRNAs
3.5K
MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...
3.5K
MicroRNAs
23.4K
MicroRNA (miRNA) are short, regulatory RNA transcribed from introns—non-coding regions of a gene—or intergenic regions—stretches of DNA present between genes. Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After...
23.4K
Leaky Scanning
5.5K
During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA. Marilyn Kozak discovered that the sequence RCCAUGG (where R...
5.5K
Nonsense-mediated mRNA Decay
11.4K
The Upf proteins that carry out nonsense-mediated decay (NMD) are found in all eukaryotic organisms, including humans. Each protein has an individual role, but they need to work in collaboration. Upf1 is an ATP-dependent RNA helicase that unwinds the RNA helix. Because Upf1 can unwind any RNA, Upf2 and Upf3 are required to help Upf1 discriminate between nonsense and normal mRNAs.
Usually, Upf3 binds to an Exon Junction Complex (EJC) at mRNA splice sites. If a ribosome fully translates the mRNA,...
Usually, Upf3 binds to an Exon Junction Complex (EJC) at mRNA splice sites. If a ribosome fully translates the mRNA,...
11.4K
Regulated mRNA Transport
6.7K
In eukaryotes, transcription and translation are compartmentalized; an mRNA is first synthesized in the nucleus and then selectively transported to the cytoplasm for protein synthesis. Before transport, a pre-mRNA undergoes several steps of post-transcriptional modifications including splicing, 5' capping, and the addition of a poly-adenine tail. Various proteins bind to the pre-mRNA during these modifications. The mRNA transport takes place with the help of multiple proteins playing...
6.7K
Regulation of Expression Occurs at Multiple Steps
25.0K
Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
25.0K


