Targeting TCF21-TCF3 heterodimer in tumor-associated pericytes attenuates hematogenous metastasis by restoring pericyte gatekeeper function.

ABSTRACT: Hematogenous metastasis is the leading cause of cancer mortality, with dysfunction of pericytes, key components of tumor vessels, playing a central role in facilitating metastatic spread. Although anti-pericyte therapies are gaining recognition for treating metastasis, current strategies that directly eliminate tumor pericytes (TPCs) may increase vascular leakiness, which paradoxically promotes further metastasis. Here, we identify a TPC-specific transcription factor heterodimer, TCF21-TCF3, which drives metastasis by enhancing collagen hydroxylation and extracellular matrix deposition. Based on the TCF21 residues that interact with TCF3, we rationally design a peptide to disrupt their dimerization and downregulate TCF21-TCF3-dependent collagen deposition. Notably, in murine models of colo

SUBMITTER: Yin W 

PROVIDER: S-EPMC12866088 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature