SMAD3
Overview
SMAD3 is a transcriptional mediator of TGF-beta signaling. Upon TGF-beta receptor activation, SMAD3 is phosphorylated, forms complexes with SMAD4, and translocates to the nucleus to regulate target gene expression. In colorectal cancer, SMAD3 and SMAD4 function as tumor suppressors, and somatic mutations in either gene can disable TGF-beta-mediated growth control. Loss or mutation of SMAD3 in the metastatic setting may confer selective advantage for invasive growth.
Alterations observed in the corpus
- Missense mutation in the SMAD3 transcriptional-regulation domain identified as a metastasis-private (branch evolution) event in patient 3 of a primary-metastasis matched CRC cohort; co-occurred with a metastasis-specific SMAD4 event, suggesting convergent TGF-beta pathway disruption at the metastatic site PMID:25164765
- TGF-β-axis alteration in pancreatic ductal adenocarcinoma, augmenting SMAD4 loss as part of broader TGF-β pathway disruption (alongside TGFBR1, TGFBR2, TGFB1, ACVR1B, ACVR1C, SMAD6). PMID:25855536
Cancer types (linked)
- Colorectal carcinoma: metastasis-specific SMAD3 missense mutation observed; co-mutation with SMAD4 loss at the metastatic site PMID:25164765
Co-occurrence and mutual exclusivity
- Co-mutated with SMAD4 in the metastatic lesion of patient 3 in a matched CRC primary-metastasis study PMID:25164765
Therapeutic relevance
- No direct therapeutic targeting reported in the corpus.
Open questions
- Whether SMAD3 mutations in CRC metastases predict differential sensitivity to TGF-beta pathway inhibitors is not yet established.
Sources
This page was processed by crosslinker on 2026-05-14. - PMID:25855536
This page was processed by crosslinker on 2026-05-14.