Related Experiment Video

Updated: Aug 20, 2026

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
09:18

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death

Published on: December 27, 2016

Transforming growth factor-beta 1-induced apoptosis is blocked by beta 1-integrin-mediated mitogen-activated protein

Hao Zhang1, Iwata Ozaki, Toshihiko Mizuta

  • 1Division of Hepatology and Metabolism, Department of Internal Medicine, Saga Medical School, Saga University, Saga 849-8501.

Cancer Science
|November 18, 2004
PubMed

Insights

Beta 1-integrin protects human hepatoma cells from transforming growth factor-beta 1 (TGF-beta 1)-induced apoptosis by activating mitogen-activated protein (MAP) kinases. This suggests beta 1-integrin may promote hepatocellular carcinoma progression.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Cancer Research

Background:

  • Growth factors and extracellular matrices are key regulators of cellular functions.
  • The interplay between transforming growth factor-beta 1 (TGF-beta 1) and integrins in hepatic cells remains incompletely understood.

Purpose of the Study:

  • To investigate the impact of beta 1-integrin on TGF-beta 1-mediated growth regulation in hepatoma cells.
  • To elucidate the molecular mechanisms underlying beta 1-integrin's influence on TGF-beta 1-induced apoptosis.

Main Methods:

  • Human hepatoma cell lines (HepG2, Huh7, Hep3B) were stably transfected with beta 1-integrin.
  • Cells were treated with TGF-beta 1, and apoptosis was assessed.
  • The role of mitogen-activated protein (MAP) kinase pathways was examined using specific inhibitors.

Main Results:

  • TGF-beta 1 suppressed hepatoma cell growth and induced apoptosis in Hep3B and Huh7 cells.
  • Beta 1-integrin overexpression conferred protection against TGF-beta 1-induced apoptosis.
  • MAP kinase inhibitors abrogated the protective effect of beta 1-integrin, while other inhibitors were ineffective.
  • Hepatoma cells overexpressing beta 1-integrin exhibited enhanced MAP kinase activity, with sustained activation upon TGF-beta 1 treatment.

Conclusions:

  • Activated MAP kinases downstream of beta 1-integrin signaling provide a potent anti-apoptotic signal in response to TGF-beta 1 in human hepatoma cells.
  • Beta 1-integrin-mediated signaling pathways may play a significant role in the development and progression of hepatocellular carcinoma.

More Related Videos

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells06:54

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

Published on: October 27, 2020

In Vitro Cultivation Techniques for Modeling Liver Organogenesis, Building Assembloids, and Designing Synthetic Tissues using Human Cell Lines08:50

In Vitro Cultivation Techniques for Modeling Liver Organogenesis, Building Assembloids, and Designing Synthetic Tissues using Human Cell Lines

Published on: April 18, 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...
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
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...