SMAD3是抑癌基因，编码蛋白是一种转录因子，在转化生长因子β（TGF-β）信号通路中起关键作用。TGF-β信号转导控制多种生物学过程，包括细胞增殖、分化和组织稳态。SMAD信号分子在细胞因子TGF-β超家族（如TGFβ1、TGFβ2、TGFβ3、激活素和淋巴结）的结合下被膜受体丝氨酸激酶激活。TGFβ依赖性的转录的背景属性允许TGF-β途径抑制癌前状态的肿瘤发生，并促进癌症进展过程中的侵袭和转移。SMAD3胚系突变发现于Loeys-Dietz遗传综合征。SMAD3体细胞失去功能性突变和缺失已经在结直肠癌中检测到虽然发生频率较低。

SMAD3 is a transcription factor that functions as a critical effector in the transforming growth factor beta (TGFß) signal pathway. TGFß signaling controls multiple biological processes including cellular proliferation, differentiation and tissue homeostasis. SMAD signaling molecules are activated by membrane receptor serine kinases following binding of TGFß superfamily of cytokines (e.g. TGFß1, TGFß2, TGFß3, activin and nodal). Following dimerization and activation of TGFß receptors, two phosphorylated receptor-regulated SMAD proteins, including SMAD3, form a trimeric complex with a co-SMAD, such as SMAD4, to allow for binding to DNA . The SMAD trimeric complex can translocate to the nucleus and regulate TGFß-mediated gene transcription in a cell-type dependent manner specified, in part, by the availability of transcriptional co-activators and chromatin accessibility. The contextual nature of TGFß-dependent transcription allows the TGFß pathway to suppress tumorigenesis in premalignant states and promote invasiveness and metastasis during cancer progression. Germline SMAD3 mutations are found in hereditary syndromes in the Loeys-Dietz phenotypic series of diseases. Although infrequent, somatic SMAD3 loss-of-function mutations and deletions have been identified in colorectal cancer, in accordance with studies in transgenic mice. SMAD3 alterations have also been observed in various other tumor types.

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