SMAD6

Overview

SMAD6 is an inhibitory SMAD protein that negatively regulates TGF-β/BMP signalling. In pancreatic ductal adenocarcinoma, SMAD6 alterations contribute to the broader disruption of the TGF-β pathway alongside SMAD4 loss, TGFBR1/TGFBR2 mutations, and other pathway components.

Alterations observed in the corpus

• 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, SMAD3). PMID:25855536

Cancer types (linked)

• PAAD: Recurrent TGF-β pathway alteration; part of the ~19–43% SMAD4-centred TGF-β disruption landscape. PMID:25855536

Co-occurrence and mutual exclusivity

• Co-occurs with other TGF-β pathway members (SMAD4, SMAD3, TGFBR1, TGFBR2, TGFB1) in PDA. PMID:25855536

Therapeutic relevance

• No direct therapeutic targeting of SMAD6 reported in the corpus; TGF-β pathway inhibition strategies in PDA are under broader investigation.

Open questions

• Individual mutation frequency and functional consequences of SMAD6 alterations in PDA remain to be characterised.

Sources

• PMID:25855536

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