The tale of transforming growth factor-beta (TGFbeta) signaling: a soigné enigma

Arindam Chaudhury1, Philip H Howe

  • 1Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.

IUBMB Life
|September 30, 2009
PubMed

Insights

Transforming growth factor-beta (TGFbeta) acts as a tumor suppressor early in cancer but promotes metastasis later. This review explores the complex, dual role of TGFbeta signaling in carcinogenesis.

Area of Science:

  • Oncology
  • Cell Biology
  • Molecular Biology

Background:

  • Transforming growth factor-beta (TGFbeta) is a critical secreted cytokine involved in numerous physiological and pathological processes.
  • TGFbeta signaling plays a complex role in cancer development, acting as both an anti-proliferative tumor suppressor and a promoter of metastasis.

Purpose of the Study:

  • To review and elucidate the enigmatic dual role of TGFbeta signaling in carcinogenesis.
  • To highlight the transition of TGFbeta from a tumor suppressor to a metastatic promoter during cancer progression.

Main Methods:

  • This is a review article, synthesizing existing research on TGFbeta signaling in cancer.
  • Literature search and analysis of studies investigating TGFbeta's function in early and late-stage tumorigenesis.

Main Results:

  • TGFbeta exhibits antiproliferative effects in early cancer stages, suppressing tumor growth.
  • In later stages, TGFbeta can promote tumor cell invasion and metastasis via autocrine signaling loops.

Conclusions:

  • TGFbeta signaling presents a paradox in cancer, with distinct roles depending on the stage of carcinogenesis.
  • Understanding the intricate regulation of TGFbeta is crucial for developing targeted cancer therapies.

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...
Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl hydroxylase and factor...
Hedgehog Signaling Pathway02:33

Hedgehog Signaling Pathway

The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
Intracellular Signaling Affects Focal Adhesions01:17

Intracellular Signaling Affects Focal Adhesions

Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Notch Signaling Pathway03:14

Notch Signaling Pathway

The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...