Integrative Proteogenomic Analysis Revealed Immune and Lactylation-dependent Metabolic Dysregulations driving ESCC Metastasis

ABSTRACT: Metastatic ability correlates well with the malignance of esophageal squamous cell carcinoma (ESCC). Gaps remain in elucidating the multi-layered interaction networks during ESCC metastasis in the premise of lysine lactylation (Kla) is of crucial importance. Here, we performed an integrated proteogenomic and lactylomic analysis of samples from 36 metastatic ESCC patients. Results exhibited prognosis-relevant immunity-driving waves in metastatic process, and intercellular adhesion molecule 1 (ICAM1) was verified to drive the migration and invasion of ESCC cells both in vitro and in vivo. Furthermore, the ESCC proteome, complicated by Kla, showed extensive interactions with its genome and transcriptome by either cis- or trans- modes, especially for metabolic proteins. Particularly, lactylation of phosphoglycerate mutase 1 (PGAM1) K251 site reinforced its binding with actin gamma 1 (ACTG1) and increased ESCC metastatic ability. Our findings provide new insights into the systemic regulation of ESCC metastasis and novel potential therapeutic targets.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Esophagus

SUBMITTER: Ye Gao  

LAB HEAD: Ye Gao

PROVIDER: PXD063341 | Pride | 2026-10-26

REPOSITORIES: Pride