title: SMAD7: a timer of tumor progression targeting TGF-β signaling.
abstract: In the context of cancer, transforming growth factor β (TGF-β) is a cell growth suppressor; however, it is also a critical inducer of invasion and metastasis. SMAD is the important mediator of TGF-β signaling pathway, which includes receptor-regulated SMADs (R-SMADs), common-mediator SMADs (co-SMADs), and inhibitory SMADs (I-SMADs). I-SMADs block the activation of R-SMADs and co-SMADs and thus play important roles especially in the SMAD-dependent signaling. SMAD7 belongs to the I-SMADs. As an inhibitor of TGF-β signaling, SMAD7 is overexpressed in numerous cancer types and its abundance is positively correlated to the malignancy. Emerging evidence has revealed the switch-in-role of SMAD7 in cancer, from a TGF-β inhibiting protein at the early stages that facilitates proliferation to an enhancer of invasion at the late stages. This role change may be accompanied or elicited by the tumor microenvironment and/or somatic mutation. Hence, current knowledge suggests a tumor-favorable timer nature of SMAD7 in cancer progression. In this review, we summarized the advances and recent findings of SMAD7 and TGF-β signaling in cancer, followed by specific discussion on the possible factors that account for the functional changes of SMAD7.
authors.affiliation: Research Institute of Digestive Diseases, The First Affiliated Hospital of Nanchang University, 17th Yongwaizen St., Nanchang, Jiangxi, 330006, People's Republic of China.
authors.forename: Lingyu
authors.initials: L
authors.lastname: Luo
authors.forename: Nianshuang
authors.initials: N
authors.lastname: Li
authors.forename: Nonghua
authors.initials: N
authors.lastname: Lv
authors.forename: Deqiang
authors.initials: D
authors.lastname: Huang
mesh_terms: D000818:Animals; D018450:Disease Progression; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction; D051906:Smad7 Protein / Q000378:metabolism*; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D051906:Smad7 Protein; D016212:Transforming Growth Factor beta