Related Experiment Video

Updated: Jun 13, 2026

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
06:54

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells

Published on: October 27, 2020

Regulation of autophagy by transforming growth factor-β (TGF-β) signaling

Hiroshi I Suzuki1, Kunihiko Kiyono, Kohei Miyazono

  • 1Department of Molecular Pathology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.

Autophagy
|May 12, 2010
PubMed

Insights

Transforming growth factor-β (TGF-β) induces autophagy in cancer cells, mediated by Smad and JNK pathways. Autophagy enhances TGF-β

Area of Science:

  • Cell Biology
  • Cancer Research
  • Molecular Signaling

Background:

  • Transforming growth factor-β (TGF-β) signaling regulates critical cellular functions and is implicated in tumorigenesis.
  • Autophagy is a cellular stress response with a dual role in cancer, acting as both a tumor suppressor and a facilitator of cancer cell survival.
  • The interplay between TGF-β signaling and autophagy in cancer remains incompletely understood.

Purpose of the Study:

  • To investigate the role of TGF-β-induced autophagy in hepatocellular carcinoma and mammary carcinoma cells.
  • To elucidate the signaling pathways mediating TGF-β-induced autophagy.
  • To determine the functional consequences of autophagy activation on TGF-β's anti-proliferative and pro-apoptotic effects in cancer.

Main Methods:

  • Utilized hepatocellular carcinoma and mammary carcinoma cell lines.
  • Employed siRNA-mediated knockdown of autophagy genes.
  • Analyzed TGF-β signaling pathways, including Smad and JNK.
  • Assessed the expression of pro-apoptotic genes Bim and Bmf.

Main Results:

  • TGF-β was demonstrated to induce autophagy in hepatocellular and mammary carcinoma cells.
  • Autophagy induction by TGF-β was found to be mediated through the Smad and JNK signaling pathways.
  • Knockdown of autophagy genes attenuated the growth-inhibitory effects of TGF-β.
  • Autophagy activation potentiated TGF-β-induced expression of pro-apoptotic genes Bim and Bmf in hepatoma cells.

Conclusions:

  • TGF-β-induced autophagy contributes to the growth-inhibitory effects of TGF-β in cancer cells.
  • Autophagy acts in concert with other anti-proliferative pathways downstream of TGF-β signaling.
  • Understanding the regulation of autophagy by TGF-β is crucial for deciphering its bidirectional roles in tumorigenesis.

More Related Videos

Exploring the Regulation of Lipid Droplet Catabolism through Lipophagy07:20

Exploring the Regulation of Lipid Droplet Catabolism through Lipophagy

Published on: January 31, 2025

Related Concept Videos

TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
Autophagy01:27

Autophagy

Autophagy is a self-digesting process by which a cell protects itself from threats both within and outside the cell, ranging from abnormal proteins to invading bacteria. In this process, obsolete components of the cell and invading microbes are degraded by hydrolytic enzymes active in an acidic environment of the lysosomal lumen.
An autophagic pathway consists of a series of signaling events activated in response to diverse stress and physiological conditions such as food deprivation,...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR activation may...