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

Jin Dai; Yanli Ji; Wei Wang; Donghern Kim; Leonard Yenwong Fai; Lei Wang; Jia Luo; Zhuo Zhang

doi:10.1016/j.taap.2017.06.014

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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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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

Jin Dai, Yanli Ji, Wei Wang, Donghern Kim, Leonard Yenwong Fai, Lei Wang, Jia Luo and Zhuo Zhang

Toxicology and applied pharmacology, Vol.331, pp.164-173

09/15/2017

DOI: 10.1016/j.taap.2017.06.014

PMCID: PMC5567692

PMID: 28624442

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Abstract

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. •A small population of cancer-like stem cells exist in Cr(VI)-transformed cells.•Those cancer-like stem cells are low in ROS levels and resistant to apoptosis.•Those cancer-like stem cells are metabolic inactive and loss of FBP1.•Those cancer-like stem cells initiate and sustain tumor growth.•Forced expression of FBP1 inhibits tumorigenecity of those cancer-like stem cells.

Cancer stem cells

Cr(VI)

Fructose-1,6-bisphosphatase

Metabolism

Reactive oxygen species

Tumorigenesis

Details

Title: Subtitle: 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
Creators: Jin Dai - University of Kentucky
Yanli Ji - University of Kentucky
Wei Wang - University of Kentucky
Donghern Kim - University of Kentucky
Leonard Yenwong Fai - University of Kentucky
Lei Wang - University of Kentucky
Jia Luo - University of Kentucky
Zhuo Zhang - University of Kentucky
Resource Type: Journal article
Publication Details: Toxicology and applied pharmacology, Vol.331, pp.164-173
DOI: 10.1016/j.taap.2017.06.014
PMID: 28624442
PMCID: PMC5567692
NLM abbreviation: Toxicol Appl Pharmacol
ISSN: 0041-008X
eISSN: 1096-0333
Publisher: Elsevier Inc
Language: English
Date published: 09/15/2017
Academic Unit: Pathology
Record Identifier: 9984201246002771

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