初期のp21ダイナミクスのパターンは,化学療法後の増殖-老化細胞の運命を決定する
Chien-Hsiang Hsu1, Steven J Altschuler2, Lani F Wu2
1Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA.
Cell
|June 18, 2019
まとめ
化学療法によって がん細胞は増殖し続けるか 衰退するかもしれません この研究は,高レベルではなく,初期のp21タンパク質のダイナミクスが細胞の運命を予測し,驚くべき増殖の原動力を明らかにしています.
科学分野:
- 細胞生物学
- 癌の研究
- 分子腫瘍学
背景:
- 化学療法は癌細胞を殺すことを目的としていますが,非致死的な用量は細胞増殖や老化につながる可能性があります.
- 化学療法後の老化と細胞運命を決定する 遅い発達を研究するのは 難しいことです
- 早期のp21ダイナミクスの化学療法による細胞運命を決定する役割は不明である.
研究 の 目的:
- 早期のp21ダイナミクスと非致死性化学療法後の癌細胞の運命との関係を調査する.
- 細胞が老化するか増殖し続けるかを予測するp21発現の明確なパターンを特定する.
- 薬物曝露後の癌細胞増殖におけるp21の反直感的な役割を理解する.
主な方法:
- 化学療法薬の投与前,投与中,および投与後のp21タンパク質の単細胞分析
- 観察されたp21発現パターンに反応して細胞運命を追跡する (増殖対衰老).
- 初期のp21の動態と最終的な細胞結果を相関させるための統計的分析.
主要な成果:
- 初期のp21ダイナミクスの3つの異なるパターンは,特定の最終的な細胞の運命と関連していた.
- 古典的な理解とは対照的に,より低い初期のp21レベルは老化を予測し,より高いレベルは増殖を予測しました.
- p21発現の"ゴールドロックスゾーン"が特定され,わずかな増加が逆説的にがん細胞の増殖を強めた.
結論:
- 早期のp21ダイナミクスは,化学療法によって引き起こされる細胞運命を決定する上で,決定的な,直感に反する役割を果たします.
- 治療の初期にp21の発現が低ければ老化が起こり,適度なp21濃度は増殖を促す可能性があります.
- この研究は,化学療法後に発生する持続的な増殖性がん細胞の源を特定し,治療戦略に影響を与えています.
関連する概念動画
Replicative Cell Senescence
4.3K
Replicative cell senescence is a property of cells that allows them to divide a finite number of times throughout the organism's lifespan while preventing excessive proliferation. Replicative senescence is associated with the gradual loss of the telomere — short, repetitive DNA sequences found at the end of the chromosomes. Telomeres are bound by a group of proteins to form a protective cap on the ends of chromosomes. Embryonic stem cells express telomerase — an enzyme that adds...
4.3K
Fates of Pyruvate
10.5K
Pyruvate is the end product of glycolysis, where glucose is oxidized to pyruvate, simultaneously reducing NAD+ to NADH. Two molecules of ATP are also produced by substrate-level phosphorylation.
In aerobic organisms, pyruvate is metabolized via the citric acid cycle to produce reduced coenzymes NADH and FADH2. These coenzymes are then oxidized in the electron transport chain to produce ATP and, in the process, regenerate the NAD+ and FAD. As seen in some cell types and organisms, fermentation...
In aerobic organisms, pyruvate is metabolized via the citric acid cycle to produce reduced coenzymes NADH and FADH2. These coenzymes are then oxidized in the electron transport chain to produce ATP and, in the process, regenerate the NAD+ and FAD. As seen in some cell types and organisms, fermentation...
10.5K
Cells Coordinate Growth and Proliferation
5.0K
Cell size is a significant factor impacting cellular design, function, and fitness. There exists some internal coordination by which cells double their masses before division, thus, achieving homeostasis. Coordination between cell growth and proliferation depends on the checkpoints in between cell cycle phases. Loss of coordination or failure in the checkpoint mechanism can drive the cell to uncontrolled growth and loss of cellular function. Like dividing cells that coordinate cellular growth,...
5.0K
Abnormal Proliferation
5.1K
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
5.1K
Personal Choice and Fate Attributions
165
Some individuals interpret life events as a consequence of their personal choices and actions, while others believe that outcomes are dictated by fate or destiny. This divergence in perspective has been examined in psychological and cross-cultural studies, particularly in relation to religious faith and cultural beliefs about causality.Fate and Personal ResponsibilityPeople who emphasize personal responsibility view events as direct consequences of their decisions. For instance, breaking a leg...
165
Chemotherapy-Induced Nausea and Vomiting: Cannabinoids
712
Tetrahydrocannabinol (THC) is a phytocannabinoid that primarily interacts with the CB1 receptor, a type of G protein-coupled receptor (GPCR) predominantly in and around the chemoreceptor trigger zone (CTZ) and emetic center. THC also blocks the serotonin receptor activity in the dorsal vagal complex (DVC) by inhibiting serotonin release. THC exerts its anti-emetic effects through these interactions, which are beneficial for patients undergoing chemotherapy.
Two synthetic agonists of THC,...
Two synthetic agonists of THC,...
712


