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Live Cell Imaging of the TGF- β/Smad3 Signaling Pathway In Vitro and In Vivo Using an Adenovirus Reporter System
Published on: July 30, 2018
SMAD7: a timer of tumor progression targeting TGF-β signaling
Lingyu Luo1, Nianshuang Li, Nonghua Lv
1Research Institute of Digestive Diseases, The First Affiliated Hospital of Nanchang University, 17th Yongwaizen St., Nanchang, Jiangxi, 330006, People's Republic of China.
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.
Insights
SMAD7, an inhibitor of transforming growth factor β (TGF-β) signaling, shifts roles in cancer. Initially suppressing tumors, it later promotes invasion and metastasis, acting as a tumor-favorable factor.
Area of Science:
- Oncology
- Molecular Biology
- Cell Signaling
Background:
- Transforming growth factor β (TGF-β) paradoxically suppresses growth but promotes invasion/metastasis in cancer.
- SMAD proteins mediate TGF-β signaling, with inhibitory SMADs (I-SMADs) like SMAD7 regulating this pathway.
- SMAD7 overexpression correlates with malignancy, suggesting a complex role in cancer progression.
Purpose of the Study:
- To review recent findings on SMAD7 and TGF-β signaling in cancer.
- To discuss the dual role of SMAD7, from tumor suppression to invasion enhancement.
- To explore factors influencing SMAD7's functional switch in cancer.
Main Methods:
- Literature review of studies on SMAD7 and TGF-β signaling in various cancers.
- Analysis of evidence detailing SMAD7's involvement in different cancer stages.
- Discussion of potential mechanisms, including tumor microenvironment and somatic mutations.
Main Results:
- SMAD7 acts as a TGF-β inhibitor early in cancer, potentially inhibiting proliferation.
- Later in cancer progression, SMAD7 enhances invasion and metastasis.
- This functional switch is potentially influenced by the tumor microenvironment and genetic mutations.
Conclusions:
- SMAD7 exhibits a context-dependent, tumor-promoting role in advanced cancer.
- Understanding SMAD7's dynamic function is crucial for developing targeted cancer therapies.
- Further research is needed to elucidate the precise mechanisms driving SMAD7's role transition.
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