Metastasis-associated in colon cancer 1 (MACC1)

Metastasis-associated in colon cancer 1 (MACC1) is a critical regulator of tumor growth and a primary driver of metastasis, originally identified in colorectal cancer. It functions primarily as a transcription factor and transcriptional activator that induces the expression of the MET proto-oncogene, thereby activating the HGF/MET signaling pathway. This activation triggers a cascade of biological processes, including cell proliferation, migration, invasion, and the epithelial-mesenchymal transition (EMT). MACC1 is overexpressed in more than 20 types of solid tumors, where it serves as a potent prognostic biomarker for metastasis and reduced patient survival. Beyond its role in metastasis, MACC1 contributes to chemoresistance, metabolic reprogramming via the Warburg effect, and immune evasion within the tumor microenvironment. Therapeutic strategies targeting MACC1 include the use of small-molecule transcriptional inhibitors like lovastatin and rottlerin, which reduce MACC1 mRNA expression, as well as downstream pathway inhibitors like selumetinib. Despite its potential as a therapeutic target, challenges such as delivery efficiency for RNA-based inhibitors and the potential impact on its largely unknown physiological functions must be addressed.

Other names

Metastasis-associated in colon cancer-1MACC-1Metastasis-associated in colon cancer protein 1

Transcriptional inhibition of MACC1 expression and disruption of the HGF/MET signaling pathway.