Tumor-derived lactate promotes resistance to bevacizumab treatment by facilitating autophagy enhancer protein RUBCNL expression through histone H3 lysine 18 lactylation (H3K18la) in colorectal cancer

References

• 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. CA Cancer J Clin. 2021;71(3):209–249. doi: 10.3322/caac.21660
   PubMed Web of Science ®Google Scholar
• Siegel RL, Miller KD, Goding Sauer A, et al. Colorectal cancer statistics, 2020. CA A Cancer J Clin. 2020;70(3):145–164. doi: 10.3322/caac.21601
   PubMed Web of Science ®Google Scholar
• Van Cutsem E, Cervantes A, Adam R, et al. ESMO consensus guidelines for the management of patients with metastatic colorectal cancer. Ann Oncol. 2016;27(8):1386–1422. doi: 10.1093/annonc/mdw235
   PubMed Web of Science ®Google Scholar
• Jönsson K, Gröndahl G, Salö M, et al. Repeated liver resection for colorectal liver metastases: a comparison with primary liver resections concerning perioperative and long-term outcome. Gastroenterol Res Pract. 2012;2012:568214. doi: 10.1155/2012/568214
   PubMed Web of Science ®Google Scholar
• Rahbari NN, Reissfelder C, Schulze-Bergkamen H, et al. Adjuvant therapy after resection of colorectal liver metastases: the predictive value of the MSKCC clinical risk score in the era of modern chemotherapy. BMC Cancer. 2014;14(1):174. doi: 10.1186/1471-2407-14-174
   PubMedGoogle Scholar
• Tzeng CW, Aloia TA. Colorectal liver metastases. J Gastrointest Surg. 2013;17(1):195-201; quiz p.201–2. doi: 10.1007/s11605-012-2022-3
   Web of Science ®Google Scholar
• Chiche L. Prise en charge chirurgicale des métastases hépatiques des cancers colorectaux [Surgical management of hepatic metastases from colorectal cancer]. J Chir (Paris). 2003;140(2):77–89.
   PubMedGoogle Scholar
• Maeda Y, Shinohara T, Nagatsu A, et al. Long-term outcomes of conversion hepatectomy for initially unresectable colorectal liver metastases. Ann Surg Oncol. 2016;23 Suppl 2(S2):S242–8. doi: 10.1245/s10434-015-4460-0
   PubMedGoogle Scholar
• Maughan TS, Adams RA, Smith CG, et al. Addition of cetuximab to oxaliplatin-based first-line combination chemotherapy for treatment of advanced colorectal cancer: results of the randomised phase 3 MRC COIN trial. Lancet. 2011;377(9783):2103–2114. doi: 10.1016/S0140-6736(11)60613-2
   PubMed Web of Science ®Google Scholar
• Van Cutsem E, Köhne CH, Láng I, et al. Cetuximab plus irinotecan, fluorouracil, and leucovorin as first-line treatment for metastatic colorectal cancer: updated analysis of overall survival according to tumor KRAS and BRAF mutation status. J Clin Oncol. 2011;29(15):2011–2019. doi: 10.1200/JCO.2010.33.5091
   PubMed Web of Science ®Google Scholar
• Venook AP, Niedzwiecki D, Lenz HJ, et al. Effect of first-line chemotherapy combined with cetuximab or bevacizumab on overall survival in patients with KRAS wild-type advanced or metastatic colorectal cancer: arandomized clinical trial. JAMA. 2017;317(23):2392–2401. doi: 10.1001/jama.2017.7105
   PubMed Web of Science ®Google Scholar
• Tomasello G, Petrelli F, Ghidini M, et al. FOLFOXIRI plus bevacizumab as conversion therapy for patients with initially unresectable metastatic colorectal cancer: a systematic review and pooled analysis. JAMA Oncol. 2017;3(7):e170278. doi: 10.1001/jamaoncol.2017.0278
   PubMed Web of Science ®Google Scholar
• Hurwitz H. Integrating the anti-VEGF-A humanized monoclonal antibody bevacizumab with chemotherapy in advanced colorectal cancer. Clin Colorectal Cancer. 2004;4(Suppl 2):S62–8. doi: 10.3816/CCC.2004.s.010
   PubMedGoogle Scholar
• Botrel TEA, Clark LGO, Paladini L, et al. Efficacy and safety of bevacizumab plus chemotherapy compared to chemotherapy alone in previously untreated advanced or metastatic colorectal cancer: a systematic review and meta-analysis. BMC Cancer. 2016;16(1):677. doi: 10.1186/s12885-016-2734-y
   PubMedGoogle Scholar
• Benson AB, Venook AP, Al-Hawary MM, et al. Colon cancer, version 2.2021, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw. 2021;19(3):329–359. doi: 10.6004/jnccn.2021.0012
   PubMed Web of Science ®Google Scholar
• Vasudev NS, Reynolds AR. Anti-angiogenic therapy for cancer: current progress, unresolved questions and future directions. Angiogenesis. 2014;17(3):471–494. Erratum in: Angiogenesis 17(3):495-7. doi: 10.1007/s10456-014-9420-y
   PubMed Web of Science ®Google Scholar
• Garcia J, Hurwitz HI, Sandler AB, et al. Bevacizumab (avastin®) in cancer treatment: a review of 15 years of clinical experience and future outlook. Cancer Treat Rev. 2020;86:102017. doi: 10.1016/j.ctrv.2020.102017
   PubMed Web of Science ®Google Scholar
• Cao D, Hou M, Guan YS, et al. Expression of HIF-1alpha and VEGF in colorectal cancer: association with clinical outcomes and prognostic implications. BMC Cancer. 2009;9(1):432. doi: 10.1186/1471-2407-9-432
   PubMedGoogle Scholar
• Hu YL, DeLay M, Jahangiri A, et al. Hypoxia-induced autophagy promotes tumor cell survival and adaptation to antiangiogenic treatment in glioblastoma. Cancer Res. 2012;72(7):1773–1783. doi: 10.1158/0008-5472.CAN-11-3831
   PubMed Web of Science ®Google Scholar
• Selvakumaran M, Yao KS, Feldman MD, et al. Antitumor effect of the angiogenesis inhibitor bevacizumab is dependent on susceptibility of tumors to hypoxia-induced apoptosis. Biochem Pharmacol. 2008;75(3):627–638. doi: 10.1016/j.bcp.2007.09.029
   PubMed Web of Science ®Google Scholar
• Tennant DA, Durán RV, Gottlieb E. Targeting metabolic transformation for cancer therapy. Nat Rev Cancer. 2010;10(4):267–277. doi: 10.1038/nrc2817
   PubMed Web of Science ®Google Scholar
• Zhang D, Tang Z, Huang H, et al. Metabolic regulation of gene expression by histone lactylation. Nature. 2019;574(7779):575–580. doi: 10.1038/s41586-019-1678-1
   PubMed Web of Science ®Google Scholar
• Yu J, Chai P, Xie M, et al. Histone lactylation drives oncogenesis by facilitating m6A reader protein YTHDF2 expression in ocular melanoma. Genome Biol. 2021;22(1):85. doi: 10.1186/s13059-021-02308-z
   PubMed Web of Science ®Google Scholar
• Yang J, Luo L, Zhao C, et al. A positive feedback loop between inactive VHL-triggered histone lactylation and PDGFRβ signaling drives clear cell renal cell carcinoma progression. Int J Biol Sci. 2022;18(8):3470–3483. doi: 10.7150/ijbs.73398
   PubMed Web of Science ®Google Scholar
• Xiong J, He J, Zhu J, et al. Lactylation-driven METTL3-mediated RNA m6A modification promotes immunosuppression of tumor-infiltrating myeloid cells. Mol Cell. 2022;82(9):1660–1677.e10. doi: 10.1016/j.molcel.2022.02.033
   PubMed Web of Science ®Google Scholar
• Yang Z, Yan C, Ma J, et al. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma. Nat Metab. 2023;5(1):61–79. doi: 10.1038/s42255-022-00710-w
   PubMedGoogle Scholar
• Lu ZH, Peng JH, Wang FL, et al. Bevacizumab with preoperative chemotherapy versus preoperative chemotherapy alone for colorectal cancer liver metastases: a retrospective cohort study. Medicine (Baltimore). 2016;95(35):e4767. doi: 10.1097/MD.0000000000004767
   PubMed Web of Science ®Google Scholar
• Cummins EP, Berra E, Comerford KM, et al. Prolyl hydroxylase-1 negatively regulates IkappaB kinase-beta, giving insight into hypoxia-induced NFkappaB activity. Proc Natl Acad Sci U S A. 2006;103(48):18154–18159. doi: 10.1073/pnas.0602235103
   PubMed Web of Science ®Google Scholar
• Milkiewicz M, Pugh CW, Egginton S. Inhibition of endogenous HIF inactivation induces angiogenesis in ischaemic skeletal muscles of mice. J Physiol. 2004;560(Pt 1):21–26. doi: 10.1113/jphysiol.2004.069757
   PubMed Web of Science ®Google Scholar
• Selvakumaran M, Amaravadi RK, Vasilevskaya IA, et al. Autophagy inhibition sensitizes colon cancer cells to antiangiogenic and cytotoxic therapy. Clin Cancer Res. 2013;19(11):2995–3007. doi: 10.1158/1078-0432.CCR-12-1542
   PubMed Web of Science ®Google Scholar
• Guo XL, Li D, Sun K, et al. Inhibition of autophagy enhances anticancer effects of bevacizumab in hepatocarcinoma. J Mol Med (Berl). 2013;91(4):473–483. doi: 10.1007/s00109-012-0966-0
   PubMed Web of Science ®Google Scholar
• Feng Y, Xiong Y, Qiao T, et al. Lactate dehydrogenase A: a key player in carcinogenesis and potential target in cancer therapy. Cancer Med. 2018;7(12):6124–6136. doi: 10.1002/cam4.1820
   PubMed Web of Science ®Google Scholar
• Strahl BD, Allis CD. The language of covalent histone modifications. Nature. 2000;403(6765):41–45. doi: 10.1038/47412
   PubMed Web of Science ®Google Scholar
• Dunn RK, Kingston RE. Gene regulation in the postgenomic era: technology takes the wheel. Mol Cell. 2007;28(5):708–714. doi: 10.1016/j.molcel.2007.11.022
   PubMed Web of Science ®Google Scholar
• Chi P, Allis CD, Wang GG. Covalent histone modifications–miswritten, misinterpreted and mis-erased in human cancers. Nat Rev Cancer. 2010;10(7):457–469. doi: 10.1038/nrc2876
   PubMed Web of Science ®Google Scholar
• Chen AN, Luo Y, Yang YH, et al. Lactylation, a novel metabolic reprogramming code: current status and prospects. Front Immunol. 2021;12:688910. doi: 10.3389/fimmu.2021.688910
   PubMed Web of Science ®Google Scholar
• Minchinton AI, Tannock IF. Drug penetration in solid tumours. Nat Rev Cancer. 2006;6(8):583–592. doi: 10.1038/nrc1893
   PubMed Web of Science ®Google Scholar
• Sorensen AG, Emblem KE, Polaskova P, et al. Increased survival of glioblastoma patients who respond to antiangiogenic therapy with elevated blood perfusion. Cancer Res. 2012;72(2):402–407. Erratum in: Cancer Res;72(2). doi: 10.1158/0008-5472.CAN-11-2464
   PubMed Web of Science ®Google Scholar
• Brown JM, Wilson WR. Exploiting tumour hypoxia in cancer treatment. Nat Rev Cancer. 2004;4(6):437–447. doi: 10.1038/nrc1367
   PubMed Web of Science ®Google Scholar
• Höckel M, Vaupel P. Tumor hypoxia: definitions and current clinical, biologic, and molecular aspects. J Natl Cancer Inst. 2001;93(4):266–276. doi: 10.1093/jnci/93.4.266
   PubMedGoogle Scholar
• Keunen O, Johansson M, Oudin A, et al. Anti-VEGF treatment reduces blood supply and increases tumor cell invasion in glioblastoma. Proc Natl Acad Sci U S A. 2011;108(9):3749–3754. doi: 10.1073/pnas.1014480108
   PubMed Web of Science ®Google Scholar
• Brenner A, Zuniga R, Sun JD, et al. Hypoxia-activated evofosfamide for treatment of recurrent bevacizumab-refractory glioblastoma: a phase I surgical study. Neuro Oncol. 2018;20(9):1231–1239. doi: 10.1093/neuonc/noy015
   PubMed Web of Science ®Google Scholar
• Brenner AJ, Floyd J, Fichtel L, et al. Phase 2 trial of hypoxia activated evofosfamide (TH302) for treatment of recurrent bevacizumab-refractory glioblastoma. Sci Rep. 2021;11(1):2306. doi: 10.1038/s41598-021-81841-0
   PubMed Web of Science ®Google Scholar
• Rey S, Schito L, Wouters BG, et al. Targeting hypoxia-inducible factors for antiangiogenic cancer therapy. Trends Cancer. 2017;3(7):529–541. doi: 10.1016/j.trecan.2017.05.002
   PubMed Web of Science ®Google Scholar
• Méndez-Blanco C, Fondevila F, García-Palomo A, et al. Sorafenib resistance in hepatocarcinoma: role of hypoxia-inducible factors. Exp Mol Med. 2018;50(10):1–9. doi: 10.1038/s12276-018-0159-1
   PubMed Web of Science ®Google Scholar
• Klionsky DJ. Autophagy: from phenomenology to molecular understanding in less than a decade. Nat Rev Mol Cell Biol. 2007;8(11):931–937. doi: 10.1038/nrm2245
   PubMed Web of Science ®Google Scholar
• Monkkonen T, Debnath J. Inflammatory signaling cascades and autophagy in cancer. Autophagy. 2018;14(2):190–198. doi: 10.1080/15548627.2017.1345412
   PubMed Web of Science ®Google Scholar
• Levine B, Kroemer G. Autophagy in the pathogenesis of disease. Cell. 2008;132(1):27–42. doi: 10.1016/j.cell.2007.12.018
   PubMed Web of Science ®Google Scholar
• Xie Z, Klionsky DJ. Autophagosome formation: core machinery and adaptations. Nat Cell Biol. 2007;9(10):1102–1109. doi: 10.1038/ncb1007-1102
   PubMed Web of Science ®Google Scholar
• Wu HB, Yang S, Weng HY, et al. Autophagy-induced KDR/VEGFR-2 activation promotes the formation of vasculogenic mimicry by glioma stem cells. Autophagy. 2017;13(9):1528–1542. doi: 10.1080/15548627.2017.1336277
   PubMed Web of Science ®Google Scholar
• Sun L, Xiong H, Chen L, et al. Deacetylation of ATG4B promotes autophagy initiation under starvation. Sci Adv. 2022;8(31):eabo0412. doi: 10.1126/sciadv.abo0412
   PubMed Web of Science ®Google Scholar
• Shi YH, Ding ZB, Zhou J, et al. Targeting autophagy enhances sorafenib lethality for hepatocellular carcinoma via ER stress-related apoptosis. Autophagy. 2011;7(10):1159–1172. doi: 10.4161/auto.7.10.16818
   PubMed Web of Science ®Google Scholar