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Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 2/2021

01-02-2021 | Translational Research and Biomarkers

CD36 Expression Is Associated with Cancer Aggressiveness and Energy Source in Esophageal Squamous Cell Carcinoma

Authors: Tomonori Yoshida, MD, Takehiko Yokobori, MD, PhD, Hideyuki Saito, MD, Kengo Kuriyama, MD, Yuji Kumakura, MD, PhD, Hiroaki Honjo, MD, PhD, Keigo Hara, MD, PhD, Makoto Sakai, MD, PhD, Tatsuya Miyazaki, MD, PhD, Hideru Obinata, PhD, Bilguun Erkhem-Ochir, MD, Navchaa Gombodorj, MD, PhD, Makoto Sohda, MD, PhD, Hiroshi Saeki, MD, PhD, Hiroyuki Kuwano, MD, PhD, Ken Shirabe, MD, PhD

Published in: Annals of Surgical Oncology | Issue 2/2021

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Abstract

Background

Esophageal squamous cell carcinoma (ESCC) is an important cause of cancer-related death worldwide. CD36, a long-chain fatty acid (FA) receptor, can initiate metastasis in human oral squamous cell carcinoma (SCC), and its expression is associated with poor prognosis in several cancers. The clinical significance of CD36 expression and its function in ESCC remain unknown.

Methods

We examined the clinical significance of CD36 expression in 160 ESCC samples using immunohistochemical staining. Functional analysis was performed to determine the association between CD36 and ESCC characteristics (proliferative ability, invasive ability, and energy source dependency).

Results

Thirty (18.8%) ESCC cases showed high CD36 expression, indicating a significant association with progression. CD36 suppression inhibited proliferation and invasiveness in ESCC cells. ESCC cells with CD36 suppression used specific essential amino acids (EAAs) as energy sources. Cell viability depended on FAs under CD36 expression. The viability of ESCC cells with CD36 suppression depended on EAAs but not FAs.

Conclusions

CD36 may be a good biomarker and therapeutic target in ESCC. Our data provide new insights into the basic mechanism of CD36-dependent energy utilization for ESCC survival. CD36 might be a key regulator of the dependency of FAs as energy source in ESCC cells.
Appendix
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Literature
1.
Kato H, Fukuchi M, Miyazaki T, Nakajima M, Tanaka N, Inose T, et al. Surgical treatment for esophageal cancer. Current issues. Dig Surg. 2007;24:88–95CrossRef
2.
Ohashi S, Miyamoto S, Kikuchi O, Goto T, Amanuma Y, Muto M. Recent advances from basic and clinical studies of esophageal squamous cell carcinoma. Gastroenterology. 2015;149:1700–15CrossRef
3.
Silverstein RL, Febbraio M. CD36, a scavenger receptor involved in immunity, metabolism, angiogenesis, and behavior. Sci Signal. 2009;2:re3CrossRef
4.
Samovski D, Sun J, Pietka T, Gross RW, Eckel RH, Su X, et al. Regulation of AMPK activation by CD36 links fatty acid uptake to beta-oxidation. Diabetes. 2015;64:353-9CrossRef
5.
Koonen DP, Glatz JF, Bonen A, Luiken JJ. Long-chain fatty acid uptake and FAT/CD36 translocation in heart and skeletal muscle. Biochim Biophys Acta. 2005;1736:163–80CrossRef
6.
Pepino MY, Kuda O, Samovski D, Abumrad NA. Structure-function of CD36 and importance of fatty acid signal transduction in fat metabolism. Annu Rev Nutr. 2014;34:281–303CrossRef
7.
Pascual G, Avgustinova A, Mejetta S, Martin M, Castellanos A, Attolini CS, et al. Targeting metastasis-initiating cells through the fatty acid receptor CD36. Nature. 2017;541:41–5CrossRef
8.
Hale JS, Otvos B, Sinyuk M, Alvarado AG, Hitomi M, Stoltz K, et al. Cancer stem cell-specific scavenger receptor CD36 drives glioblastoma progression. Stem Cells. 2014;32:1746–58CrossRef
9.
Watt MJ, Clark AK, Selth LA, Haynes VR, Lister N, Rebello R, et al. Suppressing fatty acid uptake has therapeutic effects in preclinical models of prostate cancer. Sci Transl Med. 2019;11
10.
Ladanyi A, Mukherjee A, Kenny HA, Johnson A, Mitra AK, Sundaresan S, et al. Adipocyte-induced CD36 expression drives ovarian cancer progression and metastasis. Oncogene. 2018;37:2285–301CrossRef
11.
Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144:646–74CrossRef
12.
Pavlova NN, Thompson CB. The emerging hallmarks of cancer metabolism. Cell Metab. 2016;23:27–47CrossRef
13.
DeBerardinis RJ, Chandel NS. Fundamentals of cancer metabolism. Sci Adv. 2016;2:e1600200PubMed
14.
Currie E, Schulze A, Zechner R, Walther TC, Farese RV, Jr. Cellular fatty acid metabolism and cancer. Cell Metab. 2013;18:153–61CrossRef
15.
Li Z, Kang Y. Lipid metabolism fuels cancer’s spread. Cell Metab. 2017;25:228–30CrossRef
16.
Nieman KM, Kenny HA, Penicka CV, Ladanyi A, Buell-Gutbrod R, Zillhardt MR, et al. Adipocytes promote ovarian cancer metastasis and provide energy for rapid tumor growth. Nat Med. 2011;17:1498–503CrossRef
17.
Nakayama A, Aoki S, Uchihashi K, Nishijima-Matsunobu A, Yamamoto M, Kakihara N, et al. Interaction between esophageal squamous cell carcinoma and adipose tissue in vitro. Am J Pathol. 2016;186:1180–94CrossRef
18.
Owen OE, Kalhan SC, Hanson RW. The key role of anaplerosis and cataplerosis for citric acid cycle function. J Biol Chem. 2002;277:30409–12CrossRef
19.
Honjo H, Kaira K, Miyazaki T, Yokobori T, Kanai Y, Nagamori S, et al. Clinicopathological significance of LAT1 and ASCT2 in patients with surgically resected esophageal squamous cell carcinoma. J Surg Oncol. 2016;113:381–9CrossRef
20.
Suzuki M, Yokobori T, Gombodorj N, Yashiro M, Turtoi A, Handa T, et al. High stromal transforming growth factor beta-induced expression is a novel marker of progression and poor prognosis in gastric cancer. J Surg Oncol. 2018;118:966–74CrossRef
21.
Yang P, Su C, Luo X, Zeng H, Zhao L, Wei L, et al. Dietary oleic acid-induced CD36 promotes cervical cancer cell growth and metastasis via up-regulation Src/ERK pathway. Cancer Lett. 2018;438:76–85CrossRef
22.
Zheng ST, Huo Q, Tuerxun A, Ma WJ, Lv GD, Huang CG, et al. The expression and activation of ERK/MAPK pathway in human esophageal cancer cell line EC9706. Mol Biol Rep. 2011;38:865–72CrossRef
23.
Jiang Y, Zhang J, Zhao J, Li Z, Chen H, Qiao Y, et al. TOPK promotes metastasis of esophageal squamous cell carcinoma by activating the Src/GSK3beta/STAT3 signaling pathway via gamma-catenin. BMC Cancer. 2019;19:1264CrossRef
24.
Birnstein E, Schattner M. Nutritional support in esophagogastric cancers. Surg Oncol Clin N Am. 2017;26:325–33CrossRef
25.
Nath A, Li I, Roberts LR, Chan C. Elevated free fatty acid uptake via CD36 promotes epithelial-mesenchymal transition in hepatocellular carcinoma. Sci Rep. 2015;5:14752CrossRef
Metadata
Title
CD36 Expression Is Associated with Cancer Aggressiveness and Energy Source in Esophageal Squamous Cell Carcinoma
Authors
Tomonori Yoshida, MD
Takehiko Yokobori, MD, PhD
Hideyuki Saito, MD
Kengo Kuriyama, MD
Yuji Kumakura, MD, PhD
Hiroaki Honjo, MD, PhD
Keigo Hara, MD, PhD
Makoto Sakai, MD, PhD
Tatsuya Miyazaki, MD, PhD
Hideru Obinata, PhD
Bilguun Erkhem-Ochir, MD
Navchaa Gombodorj, MD, PhD
Makoto Sohda, MD, PhD
Hiroshi Saeki, MD, PhD
Hiroyuki Kuwano, MD, PhD
Ken Shirabe, MD, PhD
Publication date
01-02-2021
Publisher
Springer International Publishing
Published in
Annals of Surgical Oncology / Issue 2/2021
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-020-08711-3

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