The DOI matches its Crossref record; 12 of the 12 references it cites were found in a registry or an index.
Autophagy Is Activated by TGF-β and Potentiates TGF-β–Mediated Growth Inhibition in Human Hepatocellular Carcinoma Cells
Abstract
Transforming growth factor-β (TGF-β) is a multifunctional cytokine that regulates cell growth, differentiation, and apoptosis of various types of cells. Autophagy is emerging as a critical response of normal and cancer cells to environmental changes, but the relationship between TGF-β signaling and autophagy has been poorly understood. Here, we showed that TGF-β activates autophagy in human hepatocellular carcinoma cell lines. TGF-β induced accumulation of autophagosomes and conversion of microtubule-associated protein 1 light chain 3 and enhanced the degradation rate of long-lived proteins. TGF-β increased the mRNA expression levels of BECLIN1, ATG5, ATG7, and death-associated protein kinase (DAPK). Knockdown of Smad2/3, Smad4, or DAPK, or inhibition of c-Jun NH2-terminal kinase, attenuated TGF-β–induced autophagy, indicating the involvement of both Smad and non-Smad pathway(s). TGF-β activated autophagy earlier than execution of apoptosis (6-12 versus 48 h), and reduction of autophagy genes by small interfering RNA attenuated TGF-β–mediated growth inhibition and induction of proapoptotic genes Bim and Bmf, suggesting the contribution of autophagy pathway to the growth-inhibitory effect of TGF-β. Additionally, TGF-β also induced autophagy in some mammary carcinoma cells, including MDA-MB-231 cells. These findings show that TGF-β signaling pathway activates autophagy in certain human cancer cells and that induction of autophagy is a novel aspect of biological functions of TGF-β. [Cancer Res 2009;69(23):8844–52]
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Cited by
Mechanism and medical implications of mammalian autophagy
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Autophagy-dependent cell death
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TGF-β Family Signaling in the Control of Cell Proliferation and Survival
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Autophagy in tumour immunity and therapy
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PM2.5-induced oxidative stress triggers autophagy in human lung epithelial A549 cells
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Metadata
- Authors
- Kiyono, K., Suzuki, H. I., Matsuyama, H., Morishita, Y., Komuro, A., Kano, M. R., Sugimoto, K., & Miyazono, K.
- Venue
- Cancer Research
- Published
- 2009-11-30
- Volume
- 69
- Issue
- 23
- Pages
- 8844-8852
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- OpenAlex
- W2171160911
- Cited by
- 285
- References
- 12
- FWCI
- 5.04
- Type
- journal article
- Language
- en
- Open access
- closed
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- Kiyono, K., Suzuki, H. I., Matsuyama, H., Morishita, Y., Komuro, A., Kano, M. R., Sugimoto, K., & Miyazono, K. (2009). Autophagy Is Activated by TGF-β and Potentiates TGF-β–Mediated Growth Inhibition in Human Hepatocellular Carcinoma Cells. Cancer Research. https://doi.org/10.1158/0008-5472.can-08-4401
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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