TY - JOUR
T1 - Gold-nanofève surface-enhanced Raman spectroscopy visualizes hypotaurine as a robust anti-oxidant consumed in cancer survival
AU - Shiota, Megumi
AU - Naya, Masayuki
AU - Yamamoto, Takehiro
AU - Hishiki, Takako
AU - Tani, Takeharu
AU - Takahashi, Hiroyuki
AU - Kubo, Akiko
AU - Koike, Daisuke
AU - Itoh, Mai
AU - Ohmura, Mitsuyo
AU - Kabe, Yasuaki
AU - Sugiura, Yuki
AU - Hiraoka, Nobuyoshi
AU - Morikawa, Takayuki
AU - Takubo, Keiyo
AU - Suina, Kentaro
AU - Nagashima, Hideaki
AU - Sampetrean, Oltea
AU - Nagano, Osamu
AU - Saya, Hideyuki
AU - Yamazoe, Shogo
AU - Watanabe, Hiroyuki
AU - Suematsu, Makoto
N1 - Funding Information:
The work was partly supported by JST, ERATO, Suematsu Gas Biology Project. Y.K. and Ms. Miwa Hirai are supported by Japan Agency for Medical Research and Development, Core Research for Evolutional Science and Technology (AMED-CREST), and establishment of the xenograft transplantation model using immunodeficient NOG mice was partly supported by a grant from Ajinomoto, Inc. The authors thank Ms. Miwa Hirai for her technical support of the manuscript preparation. We thank Yoshiko Naito, Tomomi Matsuura, Noriyo Hayakawa for their professional technical supports for metabolomics, and Professor Mayumi Kajimura and Dr. Ayako Yachie-Kinoshita for valuable discussion for manuscript preparation and systems biology in cancer, respectively.
Publisher Copyright:
© 2018 The Author(s).
PY - 2018/12/1
Y1 - 2018/12/1
N2 - Gold deposition with diagonal angle towards boehmite-based nanostructure creates random arrays of horse-bean-shaped nanostructures named gold-nanofève (GNF). GNF generates many electromagnetic hotspots as surface-enhanced Raman spectroscopy (SERS) excitation sources, and enables large-area visualization of molecular vibration fingerprints of metabolites in human cancer xenografts in livers of immunodeficient mice with sufficient sensitivity and uniformity. Differential screening of GNF-SERS signals in tumours and those in parenchyma demarcated tumour boundaries in liver tissues. Furthermore, GNF-SERS combined with quantum chemical calculation identified cysteine-derived glutathione and hypotaurine (HT) as tumour-dominant and parenchyma-dominant metabolites, respectively. CD44 knockdown in cancer diminished glutathione, but not HT in tumours. Mechanisms whereby tumours sustained HT under CD44-knockdown conditions include upregulation of PHGDH, PSAT1 and PSPH that drove glycolysis-dependent activation of serine/glycine-cleavage systems to provide one-methyl group for HT synthesis. HT was rapidly converted into taurine in cancer cells, suggesting that HT is a robust anti-oxidant for their survival under glutathione-suppressed conditions.
AB - Gold deposition with diagonal angle towards boehmite-based nanostructure creates random arrays of horse-bean-shaped nanostructures named gold-nanofève (GNF). GNF generates many electromagnetic hotspots as surface-enhanced Raman spectroscopy (SERS) excitation sources, and enables large-area visualization of molecular vibration fingerprints of metabolites in human cancer xenografts in livers of immunodeficient mice with sufficient sensitivity and uniformity. Differential screening of GNF-SERS signals in tumours and those in parenchyma demarcated tumour boundaries in liver tissues. Furthermore, GNF-SERS combined with quantum chemical calculation identified cysteine-derived glutathione and hypotaurine (HT) as tumour-dominant and parenchyma-dominant metabolites, respectively. CD44 knockdown in cancer diminished glutathione, but not HT in tumours. Mechanisms whereby tumours sustained HT under CD44-knockdown conditions include upregulation of PHGDH, PSAT1 and PSPH that drove glycolysis-dependent activation of serine/glycine-cleavage systems to provide one-methyl group for HT synthesis. HT was rapidly converted into taurine in cancer cells, suggesting that HT is a robust anti-oxidant for their survival under glutathione-suppressed conditions.
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U2 - 10.1038/s41467-018-03899-1
DO - 10.1038/s41467-018-03899-1
M3 - Article
C2 - 29674746
AN - SCOPUS:85045910060
SN - 2041-1723
VL - 9
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 1561
ER -