ATP Citrate Lyase is a General Tumour Biomarker and Contributes to the Development of Cutaneous Squamous Cell Carcinoma

Overview

Journal Acta Derm Venereol

Specialty Dermatology

Date 2024 Apr 9

PMID 38590175

Authors

Ruiting Luo

Yingjian Huang

Ruimin Bai

Meng Liu

Liang Sun

Xiaofei Wang

Yan Zheng

Affiliations

Soon will be listed here.

Abstract

ATP citrate lyase, the first rate-limiting enzyme in de novo lipogenesis, plays a crucial role in tumour progression. This study explores ATP citrate lyase's potential as a tumour biomarker and its role in cutaneous squamous cell carcinoma. ATP citrate lyase expression patterns were analysed using TCGA and TIMER databases, and patient skin specimens were collected for immunohistochemistry to determine ATP citrate lyase levels. Cell proliferation, cell cycle, apoptosis, and c-Myc expression were assessed in A431 and SCL-1 cells. Stable cell lines with reduced ATP citrate lyase expression were obtained and subcutaneously implanted into nude mice to evaluate in vivo tumour growth. Ki67, c-Myc expression and TUNEL staining were analysed in subcutaneous tumours. ATP citrate lyase exhibited upregulation in various tumours, and showed significant associations with prognosis and immune infiltrate. Moreover, ATP citrate lyase was highly expressed in cutaneous squamous cell carcinoma. After ATP citrate lyase silencing, cutaneous squamous cell carcinoma cell growth decelerated, the cell cycle halted, cell apoptosis increased, and c-Myc expression decreased. Animal experiments revealed that, following ATP citrate lyase knockdown, tumour tissue growth slowed down, and there was a reduction in Ki-67 and c-Myc expression, accompanied by enhanced TUNEL staining. In conclusion, ATP citrate lyase may serve as a tumour biomarker. It is highly expressed in cutaneous squamous cell carcinoma and may serve as a therapeutic target.

References

Zhang C, Liu J, Huang G, Zhao Y, Yue X, Wu H . Cullin3-KLHL25 ubiquitin ligase targets ACLY for degradation to inhibit lipid synthesis and tumor progression. Genes Dev. 2016; 30(17):1956-70. PMC: 5066239. DOI: 10.1101/gad.283283.116. View

Dhanasekaran R, Deutzmann A, Mahauad-Fernandez W, Hansen A, Gouw A, Felsher D . The MYC oncogene - the grand orchestrator of cancer growth and immune evasion. Nat Rev Clin Oncol. 2021; 19(1):23-36. PMC: 9083341. DOI: 10.1038/s41571-021-00549-2. View

Li C, Xiao L, Jia J, Li F, Wang X, Duan Q . Cornulin Is Induced in Psoriasis Lesions and Promotes Keratinocyte Proliferation via Phosphoinositide 3-Kinase/Akt Pathways. J Invest Dermatol. 2018; 139(1):71-80. DOI: 10.1016/j.jid.2018.06.184. View

Guo W, Ma J, Yang Y, Guo S, Zhang W, Zhao T . ATP-Citrate Lyase Epigenetically Potentiates Oxidative Phosphorylation to Promote Melanoma Growth and Adaptive Resistance to MAPK Inhibition. Clin Cancer Res. 2020; 26(11):2725-2739. DOI: 10.1158/1078-0432.CCR-19-1359. View

Stine Z, Walton Z, Altman B, Hsieh A, Dang C . MYC, Metabolism, and Cancer. Cancer Discov. 2015; 5(10):1024-39. PMC: 4592441. DOI: 10.1158/2159-8290.CD-15-0507. View

Adorno-Cruz V, Hoffmann A, Liu X, Dashzeveg N, Taftaf R, Wray B . promotes expression of and in enhancing breast cancer stemness and metastasis. Genes Dis. 2021; 8(4):493-508. PMC: 8209312. DOI: 10.1016/j.gendis.2020.01.015. View

Chang M, Azin M, Demehri S . Cutaneous Squamous Cell Carcinoma: The Frontier of Cancer Immunoprevention. Annu Rev Pathol. 2022; 17:101-119. DOI: 10.1146/annurev-pathol-042320-120056. View

Huang S, Tsai C, Kuo C, Li Y, Cheng S . ACLY inhibitors induce apoptosis and potentiate cytotoxic effects of sorafenib in thyroid cancer cells. Endocrine. 2022; 78(1):85-94. DOI: 10.1007/s12020-022-03124-6. View

Thorsson V, Gibbs D, Brown S, Wolf D, Bortone D, Yang T . The Immune Landscape of Cancer. Immunity. 2018; 48(4):812-830.e14. PMC: 5982584. DOI: 10.1016/j.immuni.2018.03.023. View

10.

Menendez J, Lupu R . Fatty acid synthase and the lipogenic phenotype in cancer pathogenesis. Nat Rev Cancer. 2007; 7(10):763-77. DOI: 10.1038/nrc2222. View

11.

Ascencao K, Dilek N, Augsburger F, Panagaki T, Zuhra K, Szabo C . Pharmacological induction of mesenchymal-epithelial transition via inhibition of H2S biosynthesis and consequent suppression of ACLY activity in colon cancer cells. Pharmacol Res. 2021; 165:105393. DOI: 10.1016/j.phrs.2020.105393. View

12.

Beckner M, Fellows-Mayle W, Zhang Z, Agostino N, Kant J, Day B . Identification of ATP citrate lyase as a positive regulator of glycolytic function in glioblastomas. Int J Cancer. 2009; 126(10):2282-95. PMC: 2847004. DOI: 10.1002/ijc.24918. View

13.

Zhang Q, Yin X, Pan Z, Cao Y, Han S, Gao G . Identification of potential diagnostic and prognostic biomarkers for prostate cancer. Oncol Lett. 2019; 18(4):4237-4245. PMC: 6757266. DOI: 10.3892/ol.2019.10765. View

14.

Osugi J, Yamaura T, Muto S, Okabe N, Matsumura Y, Hoshino M . Prognostic impact of the combination of glucose transporter 1 and ATP citrate lyase in node-negative patients with non-small lung cancer. Lung Cancer. 2015; 88(3):310-8. DOI: 10.1016/j.lungcan.2015.03.004. View

15.

Icard P, Wu Z, Fournel L, Coquerel A, Lincet H, Alifano M . ATP citrate lyase: A central metabolic enzyme in cancer. Cancer Lett. 2019; 471:125-134. DOI: 10.1016/j.canlet.2019.12.010. View

16.

Johansen C . Generation and Culturing of Primary Human Keratinocytes from Adult Skin. J Vis Exp. 2017; (130). PMC: 5755678. DOI: 10.3791/56863. View

17.

Manyam B, Garsa A, Chin R, Reddy C, Gastman B, Thorstad W . A multi-institutional comparison of outcomes of immunosuppressed and immunocompetent patients treated with surgery and radiation therapy for cutaneous squamous cell carcinoma of the head and neck. Cancer. 2017; 123(11):2054-2060. DOI: 10.1002/cncr.30601. View

18.

Pinheiro C, Longatto-Filho A, Scapulatempo C, Ferreira L, Martins S, Pellerin L . Increased expression of monocarboxylate transporters 1, 2, and 4 in colorectal carcinomas. Virchows Arch. 2008; 452(2):139-46. DOI: 10.1007/s00428-007-0558-5. View

19.

Hatzivassiliou G, Zhao F, Bauer D, Andreadis C, Shaw A, Dhanak D . ATP citrate lyase inhibition can suppress tumor cell growth. Cancer Cell. 2005; 8(4):311-21. DOI: 10.1016/j.ccr.2005.09.008. View

20.

Corchado-Cobos R, Garcia-Sancha N, Gonzalez-Sarmiento R, Perez-Losada J, Canueto J . Cutaneous Squamous Cell Carcinoma: From Biology to Therapy. Int J Mol Sci. 2020; 21(8). PMC: 7216042. DOI: 10.3390/ijms21082956. View