Hyaluronan production regulates metabolic and cancer stem-like properties of breast cancer cells via hexosamine biosynthetic pathway-coupled HIF-1 signaling

Cancer stem cells (CSCs) represent a small subpopulation of self-renewing oncogenic cells. As in many other stem cells, metabolic reprogramming has been implicated to be a key characteristic of CSCs. However, little is known about how the metabolic features of cancer cells are controlled to orchestr...

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Main Authors: Chanmee T., Ontong P., Izumikawa T., Higashide M., Mochizuki N., Chokchaitaweesuk C., Khansai M., Nakajima K., Kakizaki I., Kongtawelert P., Taniguchi N., Itano N.
Format: Journal
Published: 2017
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http://cmuir.cmu.ac.th/jspui/handle/6653943832/41349
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Institution: Chiang Mai University
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spelling th-cmuir.6653943832-413492017-09-28T04:20:51Z Hyaluronan production regulates metabolic and cancer stem-like properties of breast cancer cells via hexosamine biosynthetic pathway-coupled HIF-1 signaling Chanmee T. Ontong P. Izumikawa T. Higashide M. Mochizuki N. Chokchaitaweesuk C. Khansai M. Nakajima K. Kakizaki I. Kongtawelert P. Taniguchi N. Itano N. Cancer stem cells (CSCs) represent a small subpopulation of self-renewing oncogenic cells. As in many other stem cells, metabolic reprogramming has been implicated to be a key characteristic of CSCs. However, little is known about how the metabolic features of cancer cells are controlled to orchestrate their CSC-like properties. We recently demonstrated that hyaluronan (HA) overproduction allowed plastic cancer cells to revert to stem cell states. Here, we adopted stable isotope-Assisted tracing and mass spectrometry profiling to elucidate the metabolic features of HA-overproducing breast cancer cells. These integrated approaches disclosed an acceleration of metabolic flux in the hexosamine biosynthetic pathway (HBP). A metabolic shift toward glycolysis was also evident by quantitative targeted metabolomics, which was validated by the expression profiles of key glycolytic enzymes. Forced expression of glutamine:fructose- 6-phosphate amidotransferase 1 (GFAT1), an HBP ratelimiting enzyme, resembled the results of HA overproduction with regard to HIF-1αaccumulation and glycolytic program, whereas GFAT1 inhibition significantly decreased HIF-1α protein level in HA-overproducing cancer cells. Moreover, inhibition of the HBP-HIF-1 axis abrogated HA-driven glycolytic enhancement and reduced the CSC-like subpopulation. Taken together, our results provide compelling evidence that HA production regulates the metabolic and CSC-like properties of breast cancer cells via HBP-coupled HIF-1 signaling. 2017-09-28T04:20:51Z 2017-09-28T04:20:51Z 2016-11-11 Journal 00219258 2-s2.0-84995450861 10.1074/jbc.M116.751263 https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84995450861&origin=inward http://cmuir.cmu.ac.th/jspui/handle/6653943832/41349
institution Chiang Mai University
building Chiang Mai University Library
country Thailand
collection CMU Intellectual Repository
description Cancer stem cells (CSCs) represent a small subpopulation of self-renewing oncogenic cells. As in many other stem cells, metabolic reprogramming has been implicated to be a key characteristic of CSCs. However, little is known about how the metabolic features of cancer cells are controlled to orchestrate their CSC-like properties. We recently demonstrated that hyaluronan (HA) overproduction allowed plastic cancer cells to revert to stem cell states. Here, we adopted stable isotope-Assisted tracing and mass spectrometry profiling to elucidate the metabolic features of HA-overproducing breast cancer cells. These integrated approaches disclosed an acceleration of metabolic flux in the hexosamine biosynthetic pathway (HBP). A metabolic shift toward glycolysis was also evident by quantitative targeted metabolomics, which was validated by the expression profiles of key glycolytic enzymes. Forced expression of glutamine:fructose- 6-phosphate amidotransferase 1 (GFAT1), an HBP ratelimiting enzyme, resembled the results of HA overproduction with regard to HIF-1αaccumulation and glycolytic program, whereas GFAT1 inhibition significantly decreased HIF-1α protein level in HA-overproducing cancer cells. Moreover, inhibition of the HBP-HIF-1 axis abrogated HA-driven glycolytic enhancement and reduced the CSC-like subpopulation. Taken together, our results provide compelling evidence that HA production regulates the metabolic and CSC-like properties of breast cancer cells via HBP-coupled HIF-1 signaling.
format Journal
author Chanmee T.
Ontong P.
Izumikawa T.
Higashide M.
Mochizuki N.
Chokchaitaweesuk C.
Khansai M.
Nakajima K.
Kakizaki I.
Kongtawelert P.
Taniguchi N.
Itano N.
spellingShingle Chanmee T.
Ontong P.
Izumikawa T.
Higashide M.
Mochizuki N.
Chokchaitaweesuk C.
Khansai M.
Nakajima K.
Kakizaki I.
Kongtawelert P.
Taniguchi N.
Itano N.
Hyaluronan production regulates metabolic and cancer stem-like properties of breast cancer cells via hexosamine biosynthetic pathway-coupled HIF-1 signaling
author_facet Chanmee T.
Ontong P.
Izumikawa T.
Higashide M.
Mochizuki N.
Chokchaitaweesuk C.
Khansai M.
Nakajima K.
Kakizaki I.
Kongtawelert P.
Taniguchi N.
Itano N.
author_sort Chanmee T.
title Hyaluronan production regulates metabolic and cancer stem-like properties of breast cancer cells via hexosamine biosynthetic pathway-coupled HIF-1 signaling
title_short Hyaluronan production regulates metabolic and cancer stem-like properties of breast cancer cells via hexosamine biosynthetic pathway-coupled HIF-1 signaling
title_full Hyaluronan production regulates metabolic and cancer stem-like properties of breast cancer cells via hexosamine biosynthetic pathway-coupled HIF-1 signaling
title_fullStr Hyaluronan production regulates metabolic and cancer stem-like properties of breast cancer cells via hexosamine biosynthetic pathway-coupled HIF-1 signaling
title_full_unstemmed Hyaluronan production regulates metabolic and cancer stem-like properties of breast cancer cells via hexosamine biosynthetic pathway-coupled HIF-1 signaling
title_sort hyaluronan production regulates metabolic and cancer stem-like properties of breast cancer cells via hexosamine biosynthetic pathway-coupled hif-1 signaling
publishDate 2017
url https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84995450861&origin=inward
http://cmuir.cmu.ac.th/jspui/handle/6653943832/41349
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