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Related Experiment Video

Updated: Jul 13, 2026

Spheroid Assay to Measure TGF-β-induced Invasion
09:18

Spheroid Assay to Measure TGF-β-induced Invasion

Published on: November 16, 2011

TGF-beta control of cell proliferation.

Shuan S Huang1, Jung S Huang

  • 1Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, St. Louis, Missouri 63104, USA. huangss@slu.edu

Journal of Cellular Biochemistry
|August 10, 2005
PubMed
Summary

Type V TGF-beta receptor (TbetaR-V) mediates growth inhibition by IGFBP-3 and TGF-beta. Its signaling pathways interact with other cascades, influencing TGF-beta responsiveness and potentially contributing to cancer progression.

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Published on: October 27, 2020

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Cancer Research

Background:

  • Transforming growth factor-beta (TGF-beta) is a potent inhibitor of epithelial and endothelial cell proliferation.
  • The precise signaling mechanisms of TGF-beta-induced growth inhibition are not fully elucidated.
  • Multiple signaling pathways, beyond the canonical TbetaR-I/TbetaR-II/Smad cascade, are implicated in TGF-beta's growth inhibitory functions.

Purpose of the Study:

  • To investigate the role of Type V TGF-beta receptor (TbetaR-V) in TGF-beta and IGFBP-3 mediated growth inhibition.
  • To explore the signaling pathways and endocytic mechanisms involved in TGF-beta responsiveness.
  • To understand the contribution of TbetaR-V signaling to tumorigenesis and epithelial-to-mesenchymal transition (EMT).

Main Methods:

  • Analysis of TbetaR-V co-expression with other TGF-beta receptors (TbetaR-I, TbetaR-II, TbetaR-III).
  • Investigation of TbetaR-V's role in IGFBP-3 and TGF-beta induced growth inhibition.
  • Examination of TGF-beta endocytosis pathways (clathrin- and caveolar/lipid-raft-mediated).
  • Assessment of cross-talk between TbetaR-V signaling and other receptor tyrosine kinase pathways (IR, IGF-IR, integrin, c-Met).

Main Results:

  • TbetaR-V, identical to LRP-1, mediates IGF-independent growth inhibition by IGFBP-3.
  • TbetaR-V collaborates with TbetaR-I and TbetaR-II to mediate TGF-beta-induced growth inhibition.
  • TbetaR-V signaling involves IRS proteins and Ser/Thr phosphatases and cross-talks with multiple signaling cascades.
  • TGF-beta receptor binding ratios dictate partitioning into distinct endocytic pathways, controlling cellular responsiveness.
  • Loss of TbetaR-V signaling may promote carcinoma cell escape from TGF-beta control, contributing to EMT, aggressiveness, and invasiveness.

Conclusions:

  • TbetaR-V is a critical mediator of TGF-beta and IGFBP-3 growth inhibitory signaling.
  • TGF-beta responsiveness is regulated by endocytic pathway selection, influenced by receptor binding ratios.
  • Dysregulation of TbetaR-V signaling contributes to cancer progression by promoting EMT and invasiveness.