Characterization of Metabolic Reprogramming in Head and Neck Squamous Cell Carcinoma and Application Prospects for Targeted Therapy
-
摘要:
头颈部鳞状细胞癌（HNSCC）是全球第七大常见的恶性肿瘤，其5年生存率仅为50%左右，亟需发现更有效的诊断和治疗方法。肿瘤细胞代谢重编程是HNSCC发生发展的一个关键特征，相比于正常细胞，HNSCC细胞广泛表现出糖酵解代谢、脂质代谢和氨基酸代谢的改变。这些代谢重编程不仅影响肿瘤细胞的能量供给和生物合成，还参与调节肿瘤微环境，促进HNSCC的增殖、侵袭和转移等关键生物学过程。随着对肿瘤生物学复杂性的理解逐渐深入，针对HNSCC中的代谢重编程，靶向治疗策略正在成为一种有希望的治疗方法。尽管这些代谢靶向治疗在临床前研究中表现良好，但临床应用仍需进一步验证。未来我们需要深入探讨HNSCC中更复杂的代谢重编程特征及其生物学意义，以期发现更多有效的诊断和治疗靶点，为改善HNSCC患者的预后提供新的策略。
Abstract:Head and neck squamous cell carcinoma (HNSCC) is the seventh most common malignant tumor in the world, with a 5-year survival rate of only about 50%. Thus, discovering more effective diagnostic and therapeutic approaches is an urgent need. The metabolic reprogramming of tumor cells is a key feature in the development of HNSCC, which widely exhibits alterations in glycolytic metabolism, lipid metabolism, and amino acid metabolism compared with normal cells. Metabolic reprogramming affects the energy supply and biosynthesis of tumor cells. It also participates in the regulation of the tumor microenvironment and promotes key biological processes such as proliferation, invasion, and metastasis of HNSCC. With the progressive understanding of the complexity of tumor biology, targeted-therapy strategies against metabolic reprogramming in HNSCC are emerging as a promising therapeutic approach. These metabolically targeted therapies have performed well in preclinical studies, but their clinical application requires further validation. In the future, we need to deeply explore the more complex features of metabolic reprogramming and its biological significance in HNSCC, with the aim of discovering more effective diagnostic and therapeutic targets, as well as providing new strategies to improve the prognosis of HNSCC patients.
-
Competing interests: The authors declare that they have no competing interests.利益冲突声明：所有作者均声明不存在利益冲突。作者贡献：王瑞麟、马玉秀、刘学霖：阅读收集相关文献及撰写论文张奇、王国印：修改、阅读和定稿李红玲：论文的修改和审定
-
[1] Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries[J]. CA Cancer J Clin, 2021, 71(3): 209-249. doi: 10.3322/caac.21660
[2] Chow LQM. Head and Neck Cancer[J]. N Engl J Med, 2020, 382(1): 60-72. doi: 10.1056/NEJMra1715715
[3] Huang X, Duijf PHG, Sriram S, et al. Circulating tumour DNA alterations: emerging biomarker in head and neck squamous cell carcinoma[J]. J Biomed Sci, 2023, 30(1): 65. doi: 10.1186/s12929-023-00953-z
[4] Cramer JD, Burtness B, Le QT, et al. The changing therapeutic landscape of head and neck cancer[J]. Nat Rev Clin Oncol, 2019, 16(11): 669-683. doi: 10.1038/s41571-019-0227-z
[5] Faubert B, Solmonson A, DeBerardinis RJ. Metabolic reprogramming and cancer progression[J]. Science, 2020, 368(6487): eaaw5473. doi: 10.1126/science.aaw5473
[6] Raj S, Kumar A, Kumar D. Regulation of Glycolysis in Head and Neck Cancer[J]. Adv Exp Med Biol, 2021, 1280: 219-230.
[7] Huang G, Chen S, Washio J, et al. Glycolysis-Related Gene Analyses Indicate That DEPDC1 Promotes the Malignant Progression of Oral Squamous Cell Carcinoma via the WNT/β-Catenin Signaling Pathway[J]. Int J Mol Sci, 2023, 24(3): 1992. doi: 10.3390/ijms24031992
[8] Wang Y, Li Y, Jiang L, et al. Prognostic value of glycolysis markers in head and neck squamous cell carcinoma: a meta-analysis[J]. Aging (Albany NY), 2021, 13(5): 7284-7299.
[9] Chen X, Yu J, Tian H, et al. Circle RNA hsa_circRNA_100290 serves as a ceRNA for miR-378a to regulate oral squamous cell carcinoma cells growth via Glucose transporter-1 (GLUT1) and glycolysis[J]. J Cell Physiol, 2019, 234(11): 19130-19140. doi: 10.1002/jcp.28692
[10] Boschert V, Teusch J, Müller-Richter UDA, et al. PKM2 Modulation in Head and Neck Squamous Cell Carcinoma[J]. Int J Mol Sci, 2022, 23(2): 775. doi: 10.3390/ijms23020775
[11] Chang H, Xu Q, Li J, et al. Lactate secreted by PKM2 upregulation promotes Galectin-9-mediated immunosuppression via inhibiting NF-κB pathway in HNSCC[J]. Cell Death Dis, 2021, 12(8): 725. doi: 10.1038/s41419-021-03990-4
[12] Heawchaiyaphum C, Yoshiyama H, Iizasa H, et al. Epstein-Barr Virus Promotes Oral Squamous Cell Carcinoma Stemness through the Warburg Effect[J]. Int J Mol Sci, 2023, 24(18): 14072. doi: 10.3390/ijms241814072
[13] Li N, Chamkha I, Verma G, et al. Human papillomavirus-associated head and neck squamous cell carcinoma cells rely on glycolysis and display reduced oxidative phosphorylation[J]. Front Oncol, 2024, 13: 1304106. doi: 10.3389/fonc.2023.1304106
[14] Li Z, Liu J, Que L, et al. The immunoregulatory protein B7-H3 promotes aerobic glycolysis in oral squamous carcinoma via PI3K/Akt/mTOR pathway[J]. Cancer, 2019, 10(23): 5770-5784. doi: 10.7150/jca.29838
[15] Gong X, Tang H, Yang K. PER1 suppresses glycolysis and cell proliferation in oral squamous cell carcinoma via the PER1/RACK1/PI3K signaling complex[J]. Cell Death Dis, 2021, 12(3): 276. doi: 10.1038/s41419-021-03563-5
[16] Chen X, Zhang Y, Zhu Y, et al. Metabolic reprogramming of chemoresistant cancer cells and the potential significance of metabolic regulation in the reversal of cancer chemoresistance[J]. Metabolites, 2020, 10(7): 289. doi: 10.3390/metabo10070289
[17] Haidari S, Tröltzsch M, Knösel T, et al. Fatty Acid Receptor CD36 Functions as a Surrogate Parameter for Lymph Node Metastasis in Oral Squamous Cell Carcinma[J]. Cancers (Basel), 2021, 13(16): 4125. doi: 10.3390/cancers13164125
[18] Ohyama Y, Kawamoto Y, Chiba T, et al. Differential expression of fatty acid-binding proteins and pathological implications in the progression of tongue carcinoma[J]. Mol Clin Oncol, 2014, 2(1): 19-25. doi: 10.3892/mco.2013.198
[19] Tan M, Lin X, Chen H, et al. Sterol regulatory element binding transcription factor 1 promotes proliferation and migration in head and neck squamous cell carcinoma[J]. PeerJ, 2023, 11: e15203. doi: 10.7717/peerj.15203
[20] Liu P, Wang Y, Li X, et al. Enhanced lipid biosynthesis in oral squamous cell carcinoma cancer-associated fibroblasts contributes to tumor progression: Role of IL8/AKT/p-ACLY axis[J]. Cancer Sci, 2024, 115(5): 1433-1445. doi: 10.1111/cas.16111
[21] Miao X, Wang B, Chen K, et al. Perspectives of lipid metabolism reprogramming in head and neck squamous cell carcinoma: An overview[J]. Front Oncol, 2022, 12: 1008361. doi: 10.3389/fonc.2022.1008361
[22] Luo X, Cheng C, Tan Z, et al. Emerging roles of lipid metabolism in cancer metastasis[J]. Mol Cancer, 2017, 16(1): 76. doi: 10.1186/s12943-017-0646-3
[23] Koundouros N, Poulogiannis G. Reprogramming of fatty acid metabolism in cancer[J]. Br J Cancer, 2020, 122(1): 4-22. doi: 10.1038/s41416-019-0650-z
[24] Lieu EL, Nguyen T, Rhyne S, et al. Amino acids in cancer[J]. Exp Mol Med, 2020, 52(1): 15-30. doi: 10.1038/s12276-020-0375-3
[25] Yang J, Guo Y, Seo W, et al. Targeting cellular metabolism to reduce head and neck cancer growth[J]. Sci Rep, 2019, 9(1): 4995. doi: 10.1038/s41598-019-41523-4
[26] Zhang Z, Liu R, Shuai Y, et al. ASCT2 (SLC1A5)-dependent glutamine uptake is involved in the progression of head and neck squamous cell carcinoma[J]. Br J Cancer, 2020, 122(1): 82-93. doi: 10.1038/s41416-019-0637-9
[27] Wu SL, Zha GY, Tian KB, et al. The metabolic reprogramming of γ-aminobutyrate in oral squamous cell carcinoma[J]. BMC Oral Health, 2024, 24(1): 418. doi: 10.1186/s12903-024-04174-0
[28] Mosca L, Minopoli M, Pagano M, et al. Effects of S adenosyl L methionine on the invasion and migration of head and neck squamous cancer cells and analysis of the underlying mechanisms[J]. Int J Oncol, 2020, 56(5): 1212-1224.
[29] Hu S, Zhao C, Wang Z, et al. Clinical diagnostic value of amino acids in laryngeal squamous cell carcinomas[J]. PeerJ, 2023, 11: e15469. doi: 10.7717/peerj.15469
[30] Ortiz-Pedraza Y, Muñoz-Bello JO, Ramos-Chávez LA, et al. HPV16 E6 and E7 Oncoproteins Stimulate the Glutamine Pathway Maintaining Cell Proliferation in a SNAT1-Dependent Fashion[J]. Viruses, 2023, 15(2): 324. doi: 10.3390/v15020324
[31] Zhang X, Dong Y, Zhao M, et al. ITGB2-mediated metabolic switch in CAFs promotes OSCC proliferation by oxidation of NADH in mitochondrial oxidative phosphorylation system[J]. Theranostics, 2020, 10(26): 12044-12059. doi: 10.7150/thno.47901
[32] Tang YC, Hsiao JR, Jiang SS, et al. c-MYC-directed NRF2 drives malignant progression of head and neck cancer via glucose-6-phosphate dehydrogenase and transketolase activation[J]. Theranostics, 2021, 11(11): 5232-5247. doi: 10.7150/thno.53417
[33] Yang YF, Chang YC, Tsai KW, et al. UBE2C triggers HIF-1α-glycolytic flux in head and neck squamous cell carcinoma[J]. J Cell Mol Med, 2022, 26(13): 3716-3725. doi: 10.1111/jcmm.17400
[34] Wang G, Zhang M, Cheng M, et al. Tumor microenvironment in head and neck squamous cell carcinoma: Functions and regulatory mechanisms[J]. Cancer Lett, 2021, 507: 55-69. doi: 10.1016/j.canlet.2021.03.009
[35] Domingo-Vidal M, Whitaker-Menezes D, Martos-Rus C, et al. Cigarette Smoke Induces Metabolic Reprogramming of the Tumor Stroma in Head and Neck Squamous Cell Carcinoma[J]. Mol Cancer Res, 2019, 17(9): 1893-1909. doi: 10.1158/1541-7786.MCR-18-1191
[36] Zhi Y, Wang Q, Zi M, et al. Spatial Transcriptomic and Metabolomic Landscapes of Oral Submucous Fibrosis-Derived Oral Squamous Cell Carcinoma and its Tumor Microenvironment[J]. Adv Sci (Weinh), 2024, 11(12): e2306515. doi: 10.1002/advs.202306515
[37] Li X, Jiang E, Zhao H, et al. Glycometabolic reprogramming-mediated proangiogenic phenotype enhancement of cancer-associated fibroblasts in oral squamous cell carcinoma: role of PGC-1α/PFKFB3 axis[J]. Br J Cancer, 2022, 127(3): 449-461. doi: 10.1038/s41416-022-01818-2
[38] Hsieh YT, Chen YF, Lin SC, et al. Targeting Cellular Metabolism Modulates Head and Neck Oncogenesis[J]. Int J Mol Sci, 2019, 20(16): 3960. doi: 10.3390/ijms20163960
[39] Lu H, Lu Y, Xie Y, et al. Rational combination with PDK1 inhibition overcomes cetuximab resistance in head and neck squamous cell carcinoma[J]. JCI Insight, 2019, 4(19): e131106. doi: 10.1172/jci.insight.131106
[40] Li M, Gao F, Zhao Q, et al. Tanshinone IIA inhibits oral squamous cell carcinoma via reducing Akt-c-Myc signaling-mediated aerobic glycolysis[J]. Cell Death Dis, 2020, 11(5): 381. doi: 10.1038/s41419-020-2579-9
[41] Luo J, Hong Y, Lu Y, et al. Acetyl-CoA carboxylase rewires cancer metabolism to allow cancer cells to survive inhibition of the Warburg effect by cetuximab[J]. Cancer Lett, 2017, 384: 39-49. doi: 10.1016/j.canlet.2016.09.020
[42] Mehibel M, Ortiz-Martinez F, Voelxen N, et al. Statin-induced metabolic reprogramming in head and neck cancer: a biomarker for targeting monocarboxylate transporters[J]. Sci Rep, 2018, 8(1): 16804. doi: 10.1038/s41598-018-35103-1
[43] Zhao X, Guo B, Sun W, et al. Targeting Squalene Epoxidase Confers Metabolic Vulnerability and Overcomes Chemoresistance in HNSCC[J]. Adv Sci (Weinh), 2023, 10(27): e2206878. doi: 10.1002/advs.202206878
[44] Wicker CA, Hunt BG, Krishnan S, et al. Glutaminase inhibition with telaglenastat (CB-839) improves treatment response in combination with ionizing radiation in head and neck squamous cell carcinoma models[J]. Cancer Lett, 2021, 502: 180-188. doi: 10.1016/j.canlet.2020.12.038
[45] Song A, Wu L, Zhang BX, et al. Glutamine inhibition combined with CD47 blockade enhances radiotherapy-induced ferroptosis in head and neck squamous cell carcinoma[J]. Cancer Lett, 2024, 588: 216727. doi: 10.1016/j.canlet.2024.216727
[46] Kawasaki Y, Suzuki H, Miura M, et al. LAT1 is associated with poor prognosis and radioresistance in head and neck squamous cell carcinoma[J]. Oncol Lett, 2023, 25(4): 171. doi: 10.3892/ol.2023.13757
下载:
