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Updated: Nov 11, 2025
Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
Published on: October 27, 2020
Quaking 5 suppresses TGF-β-induced EMT and cell invasion in lung adenocarcinoma
Shengjie Wang1,2,3, Xin Tong1,2, Chang Li4
1Soochow University Laboratory of Cancer Molecular Genetics, Medical College of Soochow University, Suzhou, China.
Abstract:
Quaking (QKI) proteins belong to the signal transduction and activation of RNA (STAR) family of RNA-binding proteins that have multiple functions in RNA biology. Here, we show that QKI-5 is dramatically decreased in metastatic lung adenocarcinoma (LUAD). QKI-5 overexpression inhibits TGF-β-induced epithelial-mesenchymal transition (EMT) and invasion, whereas QKI-5 knockdown has the opposite effect. QKI-5 overexpression and silencing suppresses and promotes TGF-β-stimulated metastasis in vivo, respectively. QKI-5 inhibits TGF-β-induced EMT and invasion in a TGFβR1-dependent manner. KLF6 knockdown increases TGFβR1 expression and promotes TGF-β-induced EMT, which is partly abrogated by QKI-5 overexpression. Mechanistically, QKI-5 directly interacts with the TGFβR1 3' UTR and causes post-transcriptional degradation of TGFβR1 mRNA, thereby inhibiting TGF-β-induced SMAD3 phosphorylation and TGF-β/SMAD signaling. QKI-5 is positively regulated by KLF6 at the transcriptional level. In LUAD tissues, KLF6 is lowly expressed and positively correlated with QKI-5 expression, while TGFβR1 expression is up-regulated and inversely correlated with QKI-5 expression. We reveal a novel mechanism by which KLF6 transcriptionally regulates QKI-5 and suggest that targeting the KLF6/QKI-5/TGFβR1 axis is a promising targeting strategy for metastatic LUAD.
Insights
Quaking (QKI)-5 protein levels are reduced in metastatic lung adenocarcinoma (LUAD). Restoring QKI-5 inhibits cancer cell invasion and metastasis by degrading TGFβR1 mRNA, offering a potential therapeutic target.
Area of Science:
- Molecular Biology
- Cancer Research
- RNA Biology
Background:
- Quaking (QKI) proteins are RNA-binding proteins involved in various RNA regulation processes.
- QKI-5, a member of the STAR family, plays a role in cellular signaling and RNA metabolism.
- Metastatic lung adenocarcinoma (LUAD) is a significant health concern with complex underlying molecular mechanisms.
Purpose of the Study:
- To investigate the role of QKI-5 in the progression of lung adenocarcinoma (LUAD).
- To elucidate the molecular mechanisms by which QKI-5 affects epithelial-mesenchymal transition (EMT) and metastasis.
- To identify potential therapeutic targets for metastatic LUAD based on the QKI-5 pathway.
Main Methods:
- Analysis of QKI-5 expression in LUAD tissues.
- In vitro studies involving QKI-5 overexpression and knockdown to assess effects on EMT and invasion.
- In vivo metastasis assays in mouse models.
- Investigation of the interaction between QKI-5, TGFβR1, and KLF6 using molecular biology techniques.
Main Results:
- QKI-5 expression is significantly decreased in metastatic LUAD.
- QKI-5 overexpression inhibits TGF-β-induced EMT, invasion, and metastasis, while QKI-5 knockdown promotes these processes.
- QKI-5 directly binds to TGFβR1 3' UTR, leading to its mRNA degradation and reduced TGF-β/SMAD signaling.
- KLF6 positively regulates QKI-5 transcriptionally, and this axis is dysregulated in LUAD.
Conclusions:
- QKI-5 acts as a tumor suppressor in LUAD by inhibiting TGF-β-induced metastasis.
- The KLF6/QKI-5/TGFβR1 axis represents a novel regulatory pathway in LUAD progression.
- Targeting the KLF6/QKI-5/TGFβR1 pathway holds promise for developing new therapeutic strategies for metastatic LUAD.
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