DNA repair and autophagy are distinct biological processes vital for cell survival. Although autophagy helps maintain genome stability, there is no evidence of its direct role in the repair of DNA lesions. We discovered that lysosomes process topoisomerase 1 cleavage complexes (TOP1cc) DNA lesions in vertebrates. Selective degradation of TOP1cc by autophagy directs DNA damage repair and cell survival at clinically relevant doses of topoisomerase 1 inhibitors. TOP1cc are exported from the nucleus to lysosomes through a transient alteration of the nuclear envelope and independent of the proteasome. Mechanistically, the autophagy receptor TEX264 acts as a TOP1cc sensor at DNA replication forks, triggering TOP1cc processing by the p97 ATPase and mediating the delivery of TOP1cc to lysosomes in an MRE11-nuclease- and ATR-kinase-dependent manner. We found an evolutionarily conserved role for selective autophagy in DNA repair that enables cell survival, protects genome stability, and is clinically relevant for colorectal cancer patients.
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http://dx.doi.org/10.1016/j.cell.2024.08.020 | DOI Listing |
Open Life Sci
December 2024
Department of Gastroenterology, The Ninth People's Hospital of Chongqing, No. 69, Jialing Village, Beibei District, Chognqing, 400700, China.
Colorectal cancer (CRC) is a common malignant tumor characterized by a high degree of invasiveness, and since zinc-α2 glycoprotein (ZAG) has been implicated in the progression of several malignancies, this study was designed to investigate the role of ZAG in CRC. Its expression was assessed using the GEPIA database, and short hairpin RNA (shRNA) interference was conducted to create ZAG knockdown in CRC cell lines. We also conducted lipid synthesis, cell proliferation, apoptosis, and epithelial-mesenchymal transition (EMT) experiments to elucidate the effects of ZAG expression on CRC, as well as explored the potential underlying mechanistic pathways.
View Article and Find Full Text PDFFront Oncol
December 2024
Department of Neurosurgery, Qilu Hospital of Shandong University, JiNan, China.
We report a case and follow-up of an adult male with intracranial yolk sac tumor (YST). Initially, the patient presented with abnormal high signals in the right basal ganglia on MRI, misdiagnosed as a cavernous hemangioma. However, within 2 years, the condition rapidly progressed into a large, hypervascular solid neoplasm leading to a basal ganglia hemorrhage.
View Article and Find Full Text PDFFront Oncol
December 2024
Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.
Background: For esophageal squamous cell carcinoma (ESCC), universally accepted pathological criteria for classification by differentiation degree are lacking. Tumor budding, single-cell invasion, and nuclear grade, recognized as prognostic factors in other carcinomas, have rarely been investigated for their correlation with differentiation and prognosis in ESCC. This study aims to determine if pathological findings can predict differentiation degree and prognosis in ESCC.
View Article and Find Full Text PDFFront Pediatr
December 2024
Laboratory of Translational Research, Children's Hospital of Brasília, Brasília, Brazil.
Introduction: There is consistent evidence that may be a driver gene in B-ALL and that selected cases may benefit from the use of FLT3 inhibitors. Our study was conducted to evaluate the frequency and types of FLT3 mutations in pediatric patients with B-ALL, the relative expression of this gene, and their influence on clinical evolution.
Methods: We evaluated 156 children with B-ALL treated between July 2018 and September 2023.
Ann Surg Open
December 2024
Division of Biostatistics, Department of Public Health Sciences, University of Miami, Miami, FL.
Objective: Based on current practice guidelines, we hypothesized that most patients with esophageal cancer, particularly those with locally advanced cancer, would benefit from adjuvant therapy after esophagectomy esophagectomy alone. We sought to obtain a granular estimate of patient-level risk-adjusted survival for each therapeutic option by cancer histopathology and stage.
Background: Although esophagectomy alone is now an uncommon therapy for treating locally advanced esophageal cancer, the value of adjuvant therapy after esophagectomy is unknown.
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