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Title: 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

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. - Highlights: • 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. • Thosemore » 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.« less

Authors:
; ; ; ;  [1];  [2];  [3];  [1]
  1. Department of Toxicology and Cancer Biology, 1095 Veterans Drive, University of Kentucky, Lexington, KY 40536 (United States)
  2. Center for Research on Environmental Diseases, 1095 Veterans Drive, University of Kentucky, Lexington, KY 40536 (United States)
  3. Department of Pharmacology and Nutritional Sciences, 1095 Veterans Drive, University of Kentucky, Lexington, KY 40536 (United States)
Publication Date:
OSTI Identifier:
22722928
Resource Type:
Journal Article
Journal Name:
Toxicology and Applied Pharmacology
Additional Journal Information:
Journal Volume: 331; Conference: 9. conference on recent advances in metal toxicity and carcinogenesis research, Lexington, KY (United States), 1 Oct 2016; Other Information: Copyright (c) 2017 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0041-008X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; APOPTOSIS; CELL TRANSFORMATIONS; CHROMIUM; CHRONIC EXPOSURE; LOSSES; MONOCLINIC LATTICES; NEOPLASMS; PHOSPHORUS 21; PLANT GROWTH; STEM CELLS

Citation Formats

Dai, Jin, Ji, Yanli, Wang, Wei, Kim, Donghern, Fai, Leonard Yenwong, Wang, Lei, Luo, Jia, and Zhang, Zhuo. 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. United States: N. p., 2017. Web. doi:10.1016/J.TAAP.2017.06.014.
Dai, Jin, Ji, Yanli, Wang, Wei, Kim, Donghern, Fai, Leonard Yenwong, Wang, Lei, Luo, Jia, & Zhang, Zhuo. 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. United States. doi:10.1016/J.TAAP.2017.06.014.
Dai, Jin, Ji, Yanli, Wang, Wei, Kim, Donghern, Fai, Leonard Yenwong, Wang, Lei, Luo, Jia, and Zhang, Zhuo. Fri . "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". United States. doi:10.1016/J.TAAP.2017.06.014.
@article{osti_22722928,
title = {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},
author = {Dai, Jin and Ji, Yanli and Wang, Wei and Kim, Donghern and Fai, Leonard Yenwong and Wang, Lei and Luo, Jia and Zhang, Zhuo},
abstractNote = {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. - Highlights: • 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.},
doi = {10.1016/J.TAAP.2017.06.014},
journal = {Toxicology and Applied Pharmacology},
issn = {0041-008X},
number = ,
volume = 331,
place = {United States},
year = {2017},
month = {9}
}