Researchers have uncovered a central role for Tropomodulin-2 (TMOD2) in promoting colorectal cancer (CRC) progression and liver metastasis. TMOD2 was found to be significantly upregulated in the nuclei of highly metastatic CRC cells, correlating with advanced disease and poorer patient survival.
Using advanced proteomics, tumour samples, and both in vitro and in vivo models, the study showed that TMOD2 overexpression enhances tumour growth, cell adhesion, migration, and the formation of metastatic tumours in the liver. Conversely, reducing TMOD2 levels impaired these aggressive characteristics, demonstrating its functional importance in CRC metastasis.
Clinical analysis confirmed TMOD2 protein levels strongly distinguished metastatic versus non-metastatic CRC patients, presenting a promising biomarker for disease progression. Proteomic insights identified TMOD2-associated proteins involved in cytoskeletal dynamics and cell adhesion, including STAG1 and MARCKS, which mediate TMOD2-driven pathways.
These findings shed light on TMOD2’s modulation of the cytoskeleton and adhesion processes critical for CRC cells to metastasise to the liver. The study positions TMOD2 not only as a marker of aggressive colorectal cancer but also as a promising target for novel therapeutic interventions aimed at limiting metastasis and improving patient outcomes.
Reference
Montero-Calle A et al. Deciphering the central role of TMOD2 in colorectal cancer progression and metastasis. Br J Cancer. 2025; doi: 10.1038/s41416-025-03184-1.
