CD36 Expression Is Associated with Cancer Aggressiveness and Energy Source in Esophageal Squamous Cell Carcinoma.
Biomarkers, Tumor
/ genetics
Carcinoma, Squamous Cell
/ genetics
Cell Line, Tumor
Cell Movement
Cell Proliferation
Esophageal Neoplasms
/ genetics
Esophageal Squamous Cell Carcinoma
/ genetics
Gene Expression Regulation, Neoplastic
Head and Neck Neoplasms
Humans
Mouth Neoplasms
Neoplasm Invasiveness
Prognosis
Squamous Cell Carcinoma of Head and Neck
Journal
Annals of surgical oncology
ISSN: 1534-4681
Titre abrégé: Ann Surg Oncol
Pays: United States
ID NLM: 9420840
Informations de publication
Date de publication:
Feb 2021
Feb 2021
Historique:
received:
02
09
2019
pubmed:
13
6
2020
medline:
28
4
2021
entrez:
13
6
2020
Statut:
ppublish
Résumé
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. 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). 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. 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.
Sections du résumé
BACKGROUND
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
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
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
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.
Identifiants
pubmed: 32529269
doi: 10.1245/s10434-020-08711-3
pii: 10.1245/s10434-020-08711-3
doi:
Substances chimiques
Biomarkers, Tumor
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1217-1227Subventions
Organisme : Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science
ID : 17K19893
Organisme : Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science
ID : 18K07665
Organisme : Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science
ID : 18H02877
Références
Kato H, Fukuchi M, Miyazaki T, Nakajima M, Tanaka N, Inose T, et al. Surgical treatment for esophageal cancer. Current issues. Dig Surg. 2007;24:88–95
doi: 10.1159/000101894
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;149:1700–15
doi: 10.1053/j.gastro.2015.08.054
Silverstein RL, Febbraio M. CD36, a scavenger receptor involved in immunity, metabolism, angiogenesis, and behavior. Sci Signal. 2009;2:re3
doi: 10.1126/scisignal.272re3
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;64:353-9
doi: 10.2337/db14-0582
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;1736:163–80
doi: 10.1016/j.bbalip.2005.08.018
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;34:281–303
doi: 10.1146/annurev-nutr-071812-161220
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;541:41–5
doi: 10.1038/nature20791
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;32:1746–58
doi: 10.1002/stem.1716
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
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;37:2285–301
doi: 10.1038/s41388-017-0093-z
Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144:646–74
doi: 10.1016/j.cell.2011.02.013
Pavlova NN, Thompson CB. The emerging hallmarks of cancer metabolism. Cell Metab. 2016;23:27–47
doi: 10.1016/j.cmet.2015.12.006
DeBerardinis RJ, Chandel NS. Fundamentals of cancer metabolism. Sci Adv. 2016;2:e1600200
pubmed: 27386546
Currie E, Schulze A, Zechner R, Walther TC, Farese RV, Jr. Cellular fatty acid metabolism and cancer. Cell Metab. 2013;18:153–61
doi: 10.1016/j.cmet.2013.05.017
Li Z, Kang Y. Lipid metabolism fuels cancer’s spread. Cell Metab. 2017;25:228–30
doi: 10.1016/j.cmet.2017.01.016
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;17:1498–503
doi: 10.1038/nm.2492
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;186:1180–94
doi: 10.1016/j.ajpath.2016.01.003
Owen OE, Kalhan SC, Hanson RW. The key role of anaplerosis and cataplerosis for citric acid cycle function. J Biol Chem. 2002;277:30409–12
doi: 10.1074/jbc.R200006200
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;113:381–9
doi: 10.1002/jso.24160
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;118:966–74
doi: 10.1002/jso.25217
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;438:76–85
doi: 10.1016/j.canlet.2018.09.006
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;38:865–72
doi: 10.1007/s11033-010-0178-z
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;19:1264
doi: 10.1186/s12885-019-6453-z
Birnstein E, Schattner M. Nutritional support in esophagogastric cancers. Surg Oncol Clin N Am. 2017;26:325–33
doi: 10.1016/j.soc.2016.10.003
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;5:14752
doi: 10.1038/srep14752