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PXD063945
PXD063945 is an original dataset announced via ProteomeXchange.
Dataset Summary
| Title | Lactylome Reprogramming Mediates Therapeutic Response and Resistance to Neoadjuvant Chemotherapy in Esophageal Squamous Cell Carcinoma |
| Description | Esophageal squamous cell carcinoma (ESCC) exhibits high prevalence in China and poor prognosis despite neoadjuvant chemotherapy (NACT), with significant chemoresistance development. Tumor-associated metabolic reprogramming and NACT-induced cellular stress promote lactate accumulation, which serves as a precursor for lysine lactylation (Kla), a post-translational modification (PTM) potentially regulating cancer progression. We hypothesized that systematic characterization of the lactylome in response to NACT could reveal critical molecular mechanisms underlying treatment resistance and identify new therapeutic vulnerabilities in ESCC. Herein, through comprehensive proteomics and lactylome profiling of 31 ESCC patients' tumor tissues (with/without NACT treatment), we identified 8281 proteins and 1836 Kla sites across 62 samples. NACT induced substantial lactylome alterations with 307 differentially expressed Kla sites predominantly in non-histone proteins involved in DNA damage response and metabolic pathways. Our data reveal that while NACT-induced suppression of energy metabolism coupled with upregulated HRD1 complex expression facilitated tumor cell apoptosis, activation of ribosome biogenesis and increased nucleoprotein lactylation triggered protective mechanisms contributing to chemoresistance. Mechanistically, we demonstrated that DNA damage and elevated lactate levels induced PARP1 K654 lactylation, enhancing its enzymatic activity and augmenting poly(ADP-ribosyl)ation of downstream targets, thus promoting chemotherapy resistance. This comprehensive tissue-level landscape of Kla dynamics in ESCC response to chemotherapy establishes lactylation as a critical regulatory mechanism in treatment response, potentially offering novel therapeutic targets and predictive biomarkers for personalized treatment strategies. |
| HostingRepository | iProX |
| AnnounceDate | 2025-05-14 |
| AnnouncementXML | Submission_2026-03-10_19:31:37.109.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Unsupported dataset by repository |
| PrimarySubmitter | He Huang |
| SpeciesList | scientific name: Homo sapiens; NCBI TaxID: 9606; |
| ModificationList | No PTMs are included in the dataset |
| Instrument | Q Exactive HF-X; timsTOF Pro |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|---|---|---|
| 0 | 2025-05-14 20:50:59 | ID requested | |
| ⏵ 1 | 2026-03-10 19:31:37 | announced |
Publication List
| Dataset with its publication pending |
Keyword List
| submitter keyword: lysine lactylation, PARP1, neoadjuvant chemotherapy, esophageal squamous cell carcinoma |
Contact List
| He Huang | |
|---|---|
| contact affiliation | Chinese Academy of Sciences Shanghai Institute of Materia Medica |
| contact email | hhuang.nu@gmail.com |
| lab head | |
| He Huang | |
| contact affiliation | Chinese Academy of Sciences Shanghai Institute of Materia Medica |
| contact email | hhuang.nu@gmail.com |
| dataset submitter | |
Full Dataset Link List
| iProX dataset URI |
