Related Experiment Video

Updated: Aug 6, 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

TGF-beta inhibits Akt-induced transformation in intestinal epithelial cells

Yanna Cao1, Chunyan Deng, Courtney M Townsend

  • 1Department of Surgery, The University of Texas Medical Branch, Galveston, TX 77555-0737, USA.

Surgery
|August 15, 2006
PubMed
Abstract

Insights

Transforming growth factor beta (TGF-beta) inhibits Akt-driven colorectal cancer cell growth by promoting anoikis, a form of programmed cell death. This reveals a novel tumor-suppressor role for TGF-beta in colorectal carcinogenesis.

Area of Science:

  • Cell biology
  • Cancer research
  • Molecular oncology

Background:

  • The phosphatidylinositol 3-kinase (PI3K)/Akt pathway is activated in early colorectal carcinogenesis, promoting cancer cell survival and anchorage-independent growth.
  • Transforming growth factor beta (TGF-beta), a known tumor suppressor, is inactivated during later stages of colorectal cancer development.

Purpose of the Study:

  • To investigate whether TGF-beta can inhibit Akt-induced anchorage-independent growth and anoikis resistance in intestinal epithelial cells.

Main Methods:

  • Rat intestinal epithelial cells (RIE-1) were engineered to overexpress Akt.
  • Anchorage-independent growth was assessed via soft agar colony formation and cell counting in ultralow attachment plates.
  • Anoikis induction was measured using Annexin V staining.

Main Results:

  • Overexpression of Akt in RIE-1 cells promoted anchorage-independent growth, which was attenuated by TGF-beta.
  • TGF-beta treatment induced anoikis in Akt-expressing RIE-1 cells.
  • A caspase inhibitor blocked the TGF-beta-mediated reduction in colony formation, indicating a role for apoptosis.

Conclusions:

  • TGF-beta suppresses Akt-induced anchorage-independent growth in intestinal epithelial cells, partly by enhancing anoikis.
  • These findings highlight a novel tumor-suppressor function of TGF-beta and explain the necessity of PI3K/Akt pathway activation and TGF-beta inactivation during colorectal carcinogenesis.

More Related Videos

Molecular Analysis of Endothelial-mesenchymal Transition Induced by Transforming Growth Factor-β Signaling07:49

Molecular Analysis of Endothelial-mesenchymal Transition Induced by Transforming Growth Factor-β Signaling

Published on: August 3, 2018

Live Cell Imaging of the TGF- β/Smad3 Signaling Pathway In Vitro and In Vivo Using an Adenovirus Reporter System11:06

Live Cell Imaging of the TGF- β/Smad3 Signaling Pathway In Vitro and In Vivo Using an Adenovirus Reporter System

Published on: July 30, 2018

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...
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...
Role Of Notch Signalling In Intestinal Stem Cell Renewal01:12

Role Of Notch Signalling In Intestinal Stem Cell Renewal

Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
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...
Activation and Inactivation of G Proteins01:22

Activation and Inactivation of G Proteins

Heterotrimeric G proteins are guanine nucleotide-binding proteins. As the name suggests, heterotrimeric G proteins are composed of three subunits: alpha, beta, and gamma. They remain GDP-bound or GTP-bound inside the cells and switch between inactive/active states. The Gα subunit possesses the nucleotide-binding pocket that binds guanine nucleotides and switches between GDP or GTP-bound states. In contrast, the Gꞵ and Gγ subunits are always bound together with high affinity and are together...
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...