Mapping the interactome of OSCC prognostic-associated proteins NDRG1 and PGK1 through proximity labeling using TurboID

ABSTRACT: Oral squamous cell carcinoma (OSCC) is a prevalent type of head and neck cancer, accounting for more than 90% of all oral malignancies worldwide. The identification of diagnostic and prognostic markers for OSCC is crucial for improving patient outcomes, as early detection and treatment are critical for successful management of this disease. In this regard, our group recently demonstrated that N-myc downstream-regulated gene 1 (NDRG1) and phosphoglycerate kinase 1 (PGK1) are prognostic markers in OSCC, however, little is known about the role of these proteins in OSCC development. To better understand their signaling pathways, we used TurboID-based proximity labeling to identify the interactomes of NDRG1 and PGK1 in HEK293 cells. Here, protein abundance patterns associated with three distinct time-points were utilized for protein clustering, allowing the identification of protein clusters with a “fast” or “slow” response to biotin. Functional enrichment of GO terms revealed processes mostly associated with mRNA processing for both PGK1 and NDRG1 “fast” clusters, while GO processes related to protein localization and catalytic activity were identified in PGK1 and NDRG1 “slow” clusters, respectively. A total of 65 out of 361 proteins from different clusters were also identified in neoplastic islands of OSCC tissues from our previous study. Additionally, 28 of these proteins have their gene expression associated with prognostic features such as death, metastasis and/or relapse in OSCC patients. Ultimately, our data enabled the identification of 17 previously known physical interactions and functional associations among these proteins, as well as 30 new putative interactions, characterizing a prognostic-associated interactome composed of 28 proteins. This interactome enables the prioritization of candidates that can be further explored in OSCC progression.

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Adriana Franco Paes Leme  

LAB HEAD: Adriana Franco Paes Leme

PROVIDER: PXD048046 | Pride | 2025-05-06

REPOSITORIES: Pride