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Updated: Jul 13, 2026

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

Published on: October 27, 2020

Defective TGF-beta signaling sensitizes human cancer cells to rapamycin

N Gadir1, D N Jackson, E Lee

  • 1Department of Biological Sciences, Hunter College of the City University of New York, New York, NY 10021, USA.

Oncogene
|August 19, 2007
PubMed

Insights

Transforming growth factor-beta (TGF-beta) and protein kinase Cdelta (PKCdelta) suppress rapamycin-induced cancer cell death. Blocking TGF-beta signaling or PKCdelta makes rapamycin cytotoxic, even in the presence of serum.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Signaling

Background:

  • The mammalian target of rapamycin (mTOR) pathway is crucial for cancer cell survival.
  • Rapamycin, an mTOR inhibitor, induces apoptosis in breast cancer cells without serum.
  • Serum components can suppress rapamycin's apoptotic effects, leading to cell cycle arrest.

Purpose of the Study:

  • To investigate the role of transforming growth factor-beta (TGF-beta) and protein kinase Cdelta (PKCdelta) in mediating serum-induced resistance to rapamycin.
  • To determine if targeting TGF-beta signaling can restore rapamycin's cytotoxic effects in cancer cells.

Main Methods:

  • Utilized MDA-MB-231 human breast cancer cells, serum deprivation, and rapamycin treatment.
  • Investigated the effects of TGF-beta signaling and PKCdelta inhibition on rapamycin-induced apoptosis and cell cycle arrest.
  • Examined rapamycin's effects in other cancer cell lines (BT-549, MDA-MB-468, SW-480) with defective TGF-beta signaling.

Main Results:

  • TGF-beta suppresses rapamycin-induced apoptosis in a PKCdelta-dependent manner in serum-fed cells.
  • Inhibition of TGF-beta signaling or PKCdelta renders rapamycin cytotoxic, inducing apoptosis instead of G1 arrest.
  • Cancer cells with defective TGF-beta signaling exhibit rapamycin-induced apoptosis, regardless of serum or TGF-beta presence.

Conclusions:

  • TGF-beta signaling, via PKCdelta, is a key mechanism by which serum promotes resistance to rapamycin.
  • Disrupting TGF-beta signaling or PKCdelta activity can convert rapamycin from a cytostatic to a cytotoxic agent.
  • Tumors with impaired TGF-beta signaling, common in colon and pancreatic cancers, may be particularly sensitive to mTOR-targeting therapies like rapamycin.

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