Light exposure at night disrupts host/cancer circadian regulatory dynamics: impact on the Warburg effect, lipid signaling and tumor growth prevention.
Light exposure at night disrupts host/cancer circadian regulatory dynamics: impact on the Warburg effect, lipid signaling and tumor growth prevention.
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DOI：
10.1371/journal.pone.0102776
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Davidson L
中科院分区：
文献类型：
--
作者：
Blask DE;Dauchy RT;Dauchy EM;Mao L;Hill SM;Greene MW;Belancio VP;Sauer LA;Davidson L
视交叉上核（SCN）内的中央生物钟在时间上组织和协调许多控制癌细胞增殖和肿瘤生长的过程中发挥重要作用，这些过程与每日的光/暗周期同步，可能有助于内源性癌症预防。每天构建肿瘤生物量所需的生物能量底物和分子中间体来源于有氧糖酵解（Warburg效应）和脂质代谢。利用裸鼠培养的组织分离的人类乳腺癌异种移植物，我们确定了宿主体内的循环系统因子和Warburg效应，肿瘤中亚油酸的摄取/代谢和生长信号活动在24小时的光/暗循环中由scn驱动的夜间松果体产生的抗癌激素褪黑素在昼夜节律时间结构中被动态调节、协调和整合。夜间昏暗灯光（LAN）诱导的褪黑激素抑制破坏了几种重要的癌症预防信号机制之间由昼夜节律调节的宿主/癌症平衡，导致宿主高血糖和高胰岛素血症，以及肿瘤中有氧糖酵解、脂质信号和增殖活性失控。
The central circadian clock within the suprachiasmatic nucleus (SCN) plays an important role in temporally organizing and coordinating many of the processes governing cancer cell proliferation and tumor growth in synchrony with the daily light/dark cycle which may contribute to endogenous cancer prevention. Bioenergetic substrates and molecular intermediates required for building tumor biomass each day are derived from both aerobic glycolysis (Warburg effect) and lipid metabolism. Using tissue-isolated human breast cancer xenografts grown in nude rats, we determined that circulating systemic factors in the host and the Warburg effect, linoleic acid uptake/metabolism and growth signaling activities in the tumor are dynamically regulated, coordinated and integrated within circadian time structure over a 24-hour light/dark cycle by SCN-driven nocturnal pineal production of the anticancer hormone melatonin. Dim light at night (LAN)-induced melatonin suppression disrupts this circadian-regulated host/cancer balance among several important cancer preventative signaling mechanisms, leading to hyperglycemia and hyperinsulinemia in the host and runaway aerobic glycolysis, lipid signaling and proliferative activity in the tumor.
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影响因子：
7.3
作者：
Hubbi ME;Kshitiz;Gilkes DM;Rey S;Wong CC;Luo W;Kim DH;Dang CV;Levchenko A;Semenza GL
通讯作者：
Semenza GL
影响因子：
28.2
作者：
Cantor JR;Sabatini DM
通讯作者：
Sabatini DM
影响因子：
1.3
作者：
REITER, RJ
通讯作者：
REITER, RJ
昼夜节律的代谢和能量学的融合。
DOI：
10.1126/science.1195027
发表时间：
2010-12-03
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Bass J;Takahashi JS
通讯作者：
Takahashi JS
影响因子：
11.4
作者：
Koshiji, M;Kageyama, Y;Huang, LE
通讯作者：
Huang, LE