Leucine-Rich Alpha-2-Glycoprotein 1 Promotes Metastatic Colorectal Cancer Growth Through Human Epidermal Growth Factor Receptor 3 Signaling.

ABSTRACT:

Background & aims

Therapy failure in patients with metastatic colorectal cancer (mCRC, ∼80% occur in the liver) remains an overarching challenge. Preclinical studies demonstrated that human epidermal growth factor receptor 3 (HER3) promotes colorectal cancer (CRC) cell survival, but therapies blocking the neuregulin-induced canonical HER3 signaling have made little impact in the clinic. Recent studies suggest that the liver microenvironment promotes CRC growth by activating HER3 in a neuregulin-independent fashion, thus elucidation of these mechanisms may reveal new strategies for treating patients with mCRC.

Methods

Patient-derived primary liver endothelial cells (ECs) were used to interrogate EC-CRC crosstalk. We conducted proteomic analysis to identify EC-secreted factor(

SUBMITTER: Rathore M 

PROVIDER: S-EPMC11769768 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature