SMAD2是抑癌基因，编码蛋白是一种转录因子，其在转化生长因子β（TGF-β）信号通路中作为效应物而起作用。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。SMAD2表达在结肠直肠癌、胃癌和卵巢癌中的发生率较低，与预后不良有关。值得注意的是，磷酸化的SMAD2水平的升高和降低在几种癌症类型中都与预后不良有关。SMAD2突变在结直肠癌中有被发现，SMAD2在其他各种癌症类型中较少见，如肺癌和肝细胞癌。

SMAD2 is a transcription factor that functions as an 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 SMAD2, 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. Loss of SMAD2 expression occurs at a low frequency in colorectal, gastric and ovarian cancer and correlates with poor prognosis. Notably, both elevated and decreased levels of phosphorylated SMAD2 are associated with poor prognosis in several cancer types. Although infrequent, SMAD2 mutations are found in colorectal cancer and less frequently in various other cancer types, such as lung and hepatocellular cancer.

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