Angio‐associated migratory cell protein promotes colorectal cancer progression by enhancing phosphoglycerate kinase 1 phosphorylation

TL;DR

This study shows that AAMP promotes colorectal cancer by increasing PGK1 phosphorylation, offering a new therapeutic target.

Contribution

The study reveals a novel mechanism where AAMP enhances CRC progression through PGK1 phosphorylation.

Findings

AAMP is upregulated in CRC and correlates with poor survival.

AAMP promotes CRC cell proliferation and tumor growth by enhancing PGK1 phosphorylation.

AAMP modulates immune-related pathways and proteins, suggesting dual roles in cancer progression.

Abstract

To elucidate the oncogenic role of angio‐associated migratory cell protein (AAMP) in colorectal cancer (CRC) and its mechanistic interplay with phosphoglycerate kinase 1 (PGK1). AAMP expression was analyzed in CRC and normal tissues (tissue microarrays‐immunohistochemical/Western blot). Functional impacts were assessed via siRNA knockdown and lentiviral overexpression in CRC cell lines (proliferation: CCK‐8/3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide/clonogenic assays; tumorigenesis: xenografts). Molecular mechanisms were explored through co‐immunoprecipitation, phosphorylation assays, and Ribonucleic Acid (RNA) sequencing. AAMP was significantly upregulated in CRC versus normal tissues (p < 0.05), correlating with poor patient survival. AAMP knockdown suppressed CRC cell proliferation, colony formation, and xenograft tumor growth, whereas overexpression exacerbated these phenotypes. Mechanistically, AAMP directly bound PGK1 and enhanced its phosphorylation (p‐PGK1), driving CRC proliferation. PGK1 silencing abrogated AAMP‐mediated proliferative effects. RNA sequencing revealed AAMP modulation of immune‐related pathways (Tumor Necrosis Factor, IL‐17, Jak‐STAT) and key proteins (EGFR, RPL10, NOD2), suggesting dual roles in proliferation. AAMP promotes CRC progression through PGK1 phosphorylation‐dependent metabolic activation, proposing the AAMP‐PGK1 axis as a therapeutic target for advanced CRC.

AAMP promotes CRC progression by enhancing the p‐PGK1, highlighting its novel role in CRC.

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