Loss of fructose-1,6-bisphosphatase induces glycolysis and promotes apoptosis resistance of cancer stem-like cells: an important role in hexavalent chromium-induced carcinogenesis.
Loss of fructose-1,6-bisphosphatase induces glycolysis and promotes apoptosis resistance of cancer stem-like cells: an important role in hexavalent chromium-induced carcinogenesis.
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果糖-1,6-磷酸酶的丧失会诱导糖酵解并促进癌症干细胞的凋亡耐药性：在六价铬促进的癌中的重要作用。
DOI：
10.1016/j.taap.2017.06.014
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发表时间：
2017-09-15
影响因子：
3.8
通讯作者：
Zhang Z
中科院分区：
文献类型：
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作者：
Dai J;Ji Y;Wang W;Kim D;Fai LY;Wang L;Luo J;Zhang Z
六价铬（Cr（VI））化合物被确认为肺癌的人类致癌物。我们以前的研究表明，慢性暴露于低剂量的Cr（VI）的人支气管上皮BEAS-2B细胞导致恶性细胞转化。癌症干细胞样特性的获得涉及癌症的起始。本研究已经观察到在Cr（VI）转化的细胞（BEAS-2B-Cr）中存在少量的癌干细胞样细胞（BEAS-2B-Cr-CSC）。这些BEAS-2B-Cr-CSC表现出产生活性氧（ROS）和抗凋亡的能力极低。BEAS-2B-Cr-CSC无代谢活性，如耗氧量、葡萄糖摄取、ATP产生和乳酸盐产生减少所证明。最重要的是，BEAS-2B-Cr-CSC具有更高的致瘤性，具有高水平的细胞自我更新基因Notch 1和p21。进一步的研究发现，果糖-1，6-二磷酸酶（FBP 1），一种驱动糖异生的限速酶，在BEAS-2B-Cr-CSC中丢失。FBP 1在BEAS-2B-Cr-CSC中的强制表达恢复了ROS的产生，导致细胞凋亡增加，从而抑制肿瘤发生。总之，本研究表明，FBP 1的损失是一个关键的事件，在Cr（VI）转化细胞的肿瘤发生。
Hexavalent chromium (Cr(VI)) compounds are confirmed human carcinogens for lung cancer. Our previous studies has demonstrated that chronic exposure of human bronchial epithelial BEAS-2B cells to low dose of Cr(VI) causes malignant cell transformation. The acquisition of cancer stem cell-like properties is involved in the initiation of cancers. The present study has observed that a small population of cancer stem-like cells (BEAS-2B-Cr-CSC) exists in the Cr(VI)-transformed cells (BEAS-2B-Cr). Those BEAS-2B-Cr-CSC exhibit extremely reduced capability of generating reactive oxygen species (ROS) and apoptosis resistance. BEAS-2B-Cr-CSC are metabolic inactive as evidenced by reductions in oxygen consumption, glucose uptake, ATP production, and lactate production. Most importantly, BEAS-2B-Cr-CSC are more tumorigenic with high levels of cell self-renewal genes, Notch1 and p21. Further study has found that fructose-1,6-bisphosphatase (FBP1), an rate-limiting enzyme driving glyconeogenesis, was lost in BEAS-2B-Cr-CSC. Forced expression of FBP1 in BEAS-2B-Cr-CSC restored ROS generation, resulting in increased apoptosis, leading to inhibition of tumorigenesis. In summary, the present study suggests that loss of FBP1 is a critical event in tumorigenesis of Cr(VI)-transformed cells.
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影响因子：
4
作者：
Hess, J;Angel, P;Schorpp-Kistner, M
通讯作者：
Schorpp-Kistner, M
影响因子：
20.1
作者：
Calvert JW;Jha S;Gundewar S;Elrod JW;Ramachandran A;Pattillo CB;Kevil CG;Lefer DJ
通讯作者：
Lefer DJ
影响因子：
23.9
作者：
Lagadinou, Eleni D.;Sach, Alexander;Callahan, Kevin;Rossi, Randall M.;Neering, Sarah J.;Minhajuddin, Mohammad;Ashton, John M.;Pei, Shanshan;Grose, Valerie;O'Dwyer, Kristen M.;Liesveld, Jane L.;Brookes, Paul S.;Becker, Michael W.;Jordan, Craig T.
通讯作者：
Jordan, Craig T.
影响因子：
3.7
作者：
Abel EV;Kim EJ;Wu J;Hynes M;Bednar F;Proctor E;Wang L;Dziubinski ML;Simeone DM
通讯作者：
Simeone DM
影响因子：
9
作者：
通讯作者：
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