Related Experiment Video

Updated: Mar 19, 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

14.7K

Smad4/DPC4: A barrier against tumor progression driven by RTK/Ras/Erk and Wnt/GSK3 signaling

Hadrien Demagny1, Edward M De Robertis1

  • 1Howard Hughes Medical Institute and Department of Biological Chemistry; University of California ; Los Angeles, CA USA.

Molecular & Cellular Oncology
|June 17, 2016
PubMed

Insights

Smad4, a key tumor suppressor, is not always active but regulated by RTK/MAPK and Wnt/GSK3 signaling pathways. This study explores the implications of this regulation for cancer research and therapy.

Area of Science:

  • Molecular biology
  • Cell signaling
  • Cancer research

Background:

  • Smad4 (also known as DPC4) is a critical tumor suppressor and transcription factor within the transforming growth factor-beta (TGF-β) signaling pathway.
  • Previously, Smad4 was considered to function constitutively, meaning its activity was thought to be constant.
  • Recent findings indicate that Smad4's activity and stability are dynamically regulated by external signals.

Purpose of the Study:

  • To investigate the molecular and cellular significance of Smad4 regulation by RTK/MAPK and Wnt/GSK3 signaling pathways.
  • To explore the potential therapeutic implications arising from the dynamic regulation of Smad4.
  • To provide a deeper understanding of Smad4's role beyond constitutive function in the TGF-β pathway.

Main Methods:

  • Analysis of Smad4 protein activity and stability.
  • Investigating the interplay between Smad4 and RTK/MAPK signaling.
  • Examining the cross-talk between Smad4 and Wnt/GSK3 signaling pathways.
  • Cellular assays to assess the functional consequences of Smad4 regulation.

Main Results:

  • Smad4 activity and stability are directly modulated by the RTK/MAPK signaling cascade.
  • Smad4 is also influenced by the Wnt/GSK3 signaling pathway, affecting its function.
  • These regulatory mechanisms have significant molecular and cellular consequences.
  • The findings suggest novel avenues for therapeutic intervention.

Conclusions:

  • Smad4 function is not constitutive but is actively regulated by RTK/MAPK and Wnt/GSK3 pathways.
  • Understanding these regulatory networks is crucial for comprehending Smad4's role in cellular processes and disease.
  • The identified regulatory mechanisms offer potential targets for developing new cancer therapies.
Keywords:
EGFErkFGFGSK3RasSmadTGF-βWnttumor suppressorβ-TrCP

More Related Videos

Fluorescence-based Monitoring of PAD4 Activity via a Pro-fluorescence Substrate Analog08:37

Fluorescence-based Monitoring of PAD4 Activity via a Pro-fluorescence Substrate Analog

Published on: November 5, 2014

10.4K
Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer06:51

Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer

Published on: July 21, 2018

18.8K

Related Concept Videos

mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
5.0K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

1.6K
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...
6.2K
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
6.1K
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...
9.1K
The Ras Gene02:38

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a...
7.5K