{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T08:39:01Z","timestamp":1782895141491,"version":"3.54.5"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p>\n                    Excision repair cross-complementation group 6-like (ERCC6L), also known as PICH, is a centromere-associated SNF2 family ATPase that functions as a DNA helicase essential for mitotic chromosome segregation. Emerging evidence has established its significant oncogenic role across a broad spectrum of human malignancies. This review synthesizes current knowledge on the expression landscape, oncogenic functions, molecular mechanisms, and clinical significance of ERCC6L in cancer. Pan-cancer analyses consistently demonstrate that ERCC6L is frequently overexpressed in most tumor types compared to normal tissues, driven by mechanisms such as DNA amplification and promoter hypomethylation. This upregulation strongly correlates with aggressive clinicopathological features, including advanced tumor stage, metastasis, and poor patient prognosis across cancers like breast cancer, hepatocellular carcinoma, lung adenocarcinoma, and gastric cancer. Functionally, ERCC6L acts as a potent driver of malignant phenotypes by promoting uncontrolled proliferation through cell cycle acceleration, exerting anti-apoptotic effects, and enhancing invasion and metastasis via epithelial-mesenchymal transition. Mechanistically, ERCC6L operates at the nexus of multiple cancer pathways. It interacts with key mitotic regulators including PLK1, FOXM1, and KIF4A to govern cell cycle progression, activates pro-survival signaling cascades such as PI3K\/AKT and NF-\u03baB, and drives metastasis via PJA2-mediated p53 ubiquitination in lung adenocarcinoma. Furthermore, ERCC6L promotes metabolic reprogramming by stabilizing HIF-1\u03b1 or transactivating PLK1 to drive aerobic glycolysis, and modulates DNA damage response, linking it to radio- and chemoresistance. Emerging evidence also connects ERCC6L to an immunosuppressive tumor microenvironment, with associations including Th2 cell infiltration, macrophage polarization, and reduced immune infiltration in HRD-high tumors, suggesting potential as a predictive biomarker for immunotherapy. The consistent association with aggressive tumor behavior positions ERCC6L as a valuable prognostic biomarker and a promising therapeutic target. Preclinical studies demonstrate that ERCC6L inhibition suppresses tumor growth and enhances treatment efficacy; however, current evidence is limited to\n                    <jats:italic>in vitro<\/jats:italic>\n                    and xenograft models, and substantial further validation is required before clinical translation.\n                  <\/jats:p>","DOI":"10.3389\/fonc.2026.1812829","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T07:21:36Z","timestamp":1782890496000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["ERCC6L in human cancers: oncogenic functions, molecular mechanisms, and clinical implications as a prognostic biomarker and therapeutic target"],"prefix":"10.3389","volume":"16","author":[{"given":"Lingyu","family":"Jiang","sequence":"first","affiliation":[{"name":"Intensive Care Unit, The People\u2019s Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Sciences","place":["Nanning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huaihai","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care, The People\u2019s Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Sciences","place":["Nanning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"He","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, The People\u2019s Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Sciences","place":["Nanning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junqi","family":"Qin","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, The People\u2019s Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Sciences","place":["Nanning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianwei","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, The People\u2019s Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Sciences","place":["Nanning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaping","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, The People\u2019s Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Sciences","place":["Nanning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifan","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, The People\u2019s Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Sciences","place":["Nanning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yonglong","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, The People\u2019s Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Sciences","place":["Nanning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.11.041","article-title":"Pich, a centromere-associated snf2 family atpase, is regulated by plk1 and required for the spindle checkpoint","volume":"128","author":"Baumann","year":"2007","journal-title":"Cell"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.08.071","article-title":"Loss of pich results in chromosomal instability, p53 activation, and embryonic lethality","volume":"24","author":"Albers","year":"2018","journal-title":"Cell Rep"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxlet.2005.02.013","article-title":"Ercc6l, a gene of snf2 family, may play a role in the teratogenic action of alcohol","volume":"157","author":"Xu","year":"2005","journal-title":"Toxicol Lett"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0020929","article-title":"Molecular cloning and gene expression analysis of ercc6l in sika deer (cervus nippon hortulorum)","volume":"6","author":"Yin","year":"2011","journal-title":"PloS One"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1111\/febs.70550","article-title":"Pich facilitates ipsc reprogramming by alleviating genomic instability induced by dna replication stress","author":"Zhang","year":"2026","journal-title":"FEBS J"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.14998","article-title":"Ercc6l, a dna helicase, is involved in cell proliferation and associated with survival and progress in breast and kidney cancers","volume":"8","author":"Pu","year":"2017","journal-title":"Oncotarget"},{"key":"B7","doi-asserted-by":"publisher","first-page":"1347","DOI":"10.1186\/s12885-022-10452-3","article-title":"A pan-cancer analysis of the oncogenic role of ercc6l","volume":"22","author":"Lu","year":"2022","journal-title":"BMC Cancer"},{"key":"B8","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1186\/s13046-023-02806-x","article-title":"Ercc6l facilitates the onset of mammary neoplasia and promotes the high Malignance of breast cancer by accelerating the cell cycle","volume":"42","author":"Yang","year":"2023","journal-title":"J Exp Clin Cancer Res: CR"},{"key":"B9","doi-asserted-by":"publisher","first-page":"131","DOI":"10.3892\/or.2022.8342","article-title":"Overexpression of ercc6l correlates with poor prognosis and confers Malignant phenotypes of lung adenocarcinoma","volume":"48","author":"Huang","year":"2022","journal-title":"Oncol Rep"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.18632\/aging.203387","article-title":"Ercc6l promotes cell growth and metastasis in gastric cancer through activating nf-\u03bab signaling","volume":"13","author":"Chen","year":"2021","journal-title":"Aging"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1038\/s41417-018-0064-8","article-title":"Ercc6l that is up-regulated in high grade of renal cell carcinoma enhances cell viability in vitro and promotes tumor growth in vivo potentially through modulating mapk signalling pathway","volume":"26","author":"Zhang","year":"2019","journal-title":"Cancer Gene Ther"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1002\/jgm.70012","article-title":"Characterization of immune landscape based on homologous recombination deficiency associated signatures and identification of knockdown of ercc6l to promote radiosensitivity in breast cancer","volume":"27","author":"Li","year":"2025","journal-title":"J Gene Med"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2018.9317","article-title":"Shrna knockdown of dna helicase ercc6l expression inhibits human breast cancer growth","volume":"18","author":"Liu","year":"2018","journal-title":"Mol Med Rep"},{"key":"B14","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1038\/s41419-025-07879-4","article-title":"Ercc6l-mediated stabilization of hif-1\u03b1 enhances glycolysis and stemness properties of lung adenocarcinoma cells","volume":"16","author":"Lu","year":"2025","journal-title":"Cell Death Dis"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2026.124216","article-title":"Ercc6l promotes cutaneous melanoma progression via plk1-mediated aerobic glycolysis: mechanisms and therapeutic implications","volume":"389","author":"Zhang","year":"2026","journal-title":"Life Sci"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.5306\/wjco.v13.i8.675","article-title":"Eight hub genes as potential biomarkers for breast cancer diagnosis and prognosis: a tcga-based study","volume":"13","author":"Liu","year":"2022","journal-title":"World J Clin Oncol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.21037\/jgo-20-192","article-title":"Upregulation of ercc6l is associated with tumor progression and unfavorable prognosis in hepatocellular carcinoma","volume":"11","author":"Yu","year":"2020","journal-title":"J Gastroint Oncol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-020-06277-4","article-title":"Upregulation of excision repair cross-complementation group 6-like (ercc6l) promotes tumor growth in hepatocellular carcinoma","volume":"66","author":"Zhang","year":"2021","journal-title":"Dig Dis Sci"},{"key":"B19","doi-asserted-by":"publisher","first-page":"853","DOI":"10.1186\/s12885-020-07367-2","article-title":"Ercc6l promotes the progression of hepatocellular carcinoma through activating pi3k\/akt and nf-\u03bab signaling pathway","volume":"20","author":"Chen","year":"2020","journal-title":"BMC Cancer"},{"key":"B20","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1007\/s12032-022-01654-7","article-title":"Ercc6l is a biomarker and therapeutic target for non-small cell lung adenocarcinoma","volume":"39","author":"Hou","year":"2022","journal-title":"Med Oncol (Northwood Lond Engl)"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1186\/s12931-026-03692-5","article-title":"Ercc6l drives lung adenocarcinoma metastasis: a pja2\/p53 ubiquitination-dependent mechanism","author":"Jiang","year":"2026","journal-title":"Resp Res"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2025.1541489","article-title":"Prognostic and tumor microenvironmental features of gastric cancer revealed by macrophage polarization and protein lactylation-related genes","volume":"16","author":"Xu","year":"2025","journal-title":"Front Genet"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1007\/s12094-023-03180-y","article-title":"A nine-gene signature as prognostic biomarker in gastric cancer by bioinformatics analysis","volume":"25","author":"Wang","year":"2023","journal-title":"Clin Trans Oncol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.3892\/ol.2019.10297","article-title":"Ercc6l promotes cell growth and invasion in human colorectal cancer","volume":"18","author":"Xie","year":"2019","journal-title":"Oncol Lett"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1038\/s41420-023-01314-3","article-title":"Ercc6l facilitates the progression of laryngeal squamous cell carcinoma by the binding of foxm1 and kif4a","volume":"9","author":"Cui","year":"2023","journal-title":"Cell Death Discov"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2018.00589","article-title":"Identification of potential prognostic genes for neuroblastoma","volume":"9","author":"Zhong","year":"2018","journal-title":"Front Genet"},{"key":"B27","doi-asserted-by":"publisher","first-page":"91","DOI":"10.21037\/tp-23-582","article-title":"Development and validation of a novel stemness-related prognostic model for neuroblastoma using integrated machine learning and bioinformatics analyses","volume":"13","author":"Xia","year":"2024","journal-title":"Trans Pediatr"},{"key":"B28","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1186\/s12935-018-0703-z","article-title":"Identification of biomarkers of chromophobe renal cell carcinoma by weighted gene co-expression network analysis","volume":"18","author":"Yin","year":"2018","journal-title":"Cancer Cell Int"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.31790","article-title":"Acidic extracellular environment affects mirna expression in tumors in vitro and in vivo","volume":"144","author":"Riemann","year":"2019","journal-title":"Int J Cancer"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-020-01815-4","article-title":"Impact of the acidic environment on gene expression and functional parameters of tumors in vitro and in vivo","volume":"40","author":"Rauschner","year":"2021","journal-title":"J Exp Clin Cancer Res: CR"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1002\/jbt.70049","article-title":"Anti-proliferation effect of nodosin on hepatocellular carcinoma cells via the ercc6l\/pi3k\/akt\/axis","volume":"38","author":"Wang","year":"2024","journal-title":"J Biochem Mol Tox"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1002\/ctm2.70349","article-title":"Pich deficiency attenuates the progression of lung adenocarcinoma and disrupts the dna damage response","volume":"15","author":"Miao","year":"2025","journal-title":"Clin Transl Med"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2024.1476100","article-title":"Characterization of the function and clinical value of ercc family genes in lung adenocarcinoma","volume":"14","author":"Lu","year":"2024","journal-title":"Front Oncol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1462496","article-title":"Genomic instability as a driver and suppressor of anti-tumor immunity","volume":"15","author":"Requesens","year":"2024","journal-title":"Front Immunol"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1011479","article-title":"Rad52 and ercc6l\/pich have a compensatory relationship for genome stability in mitosis","volume":"20","author":"Osia","year":"2024","journal-title":"PloS Genet"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/j.radonc.2025.111159","article-title":"Evaluation of the association between sex-linked genes and treatment response in lung cancer","volume":"212","author":"Kinsella","year":"2025","journal-title":"Radiother Oncol J Eur Soc For Ther Radiol Oncol"},{"key":"B37","doi-asserted-by":"publisher","first-page":"6255","DOI":"10.1038\/s41598-021-85498-7","article-title":"Adipose most abundant 2 protein is a predictive marker for cisplatin sensitivity in cancers","volume":"11","author":"Kamimura","year":"2021","journal-title":"Sci Rep-Uk"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2014.222","article-title":"Discovery and development of the polo-like kinase inhibitor volasertib in cancer therapy","volume":"29","author":"Gjertsen","year":"2015","journal-title":"Leukemia"},{"key":"B39","doi-asserted-by":"publisher","first-page":"517","DOI":"10.1186\/s40001-023-01511-x","article-title":"Potential 'anti-cancer' effects of esketamine on proliferation, apoptosis, migration and invasion in esophageal squamous carcinoma cells","volume":"28","author":"Li","year":"2023","journal-title":"Eur J Med Res"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2026.1812829\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T07:21:36Z","timestamp":1782890496000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2026.1812829\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,1]]},"references-count":39,"alternative-id":["10.3389\/fonc.2026.1812829"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2026.1812829","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,1]]},"article-number":"1812829"}}