Related Experiment Video

Updated: May 20, 2026

Induction of Mesenchymal-Epithelial Transitions in Sarcoma Cells
11:42

Induction of Mesenchymal-Epithelial Transitions in Sarcoma Cells

Published on: April 7, 2017

Altered death receptor signaling promotes epithelial-to-mesenchymal transition and acquired chemoresistance

James W Antoon1, Rongye Lai, Amanda P Struckhoff

  • 1Departments of Pharmacology, Tulane University School of Medicine, Tulane Avenue, New Orleans, LA, USA.

Scientific Reports
|July 31, 2012
PubMed

Insights

Acquired resistance to tumor necrosis factor (TNF) in breast cancer involves altered estrogen receptor (ER) signaling, impaired apoptosis, and increased epithelial-mesenchymal transition (EMT), leading to a more aggressive, multi-drug resistant phenotype.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Altered death receptor signaling is a key mechanism of clinical resistance to cancer therapies.
  • Understanding resistance to chemotherapy in breast cancer is crucial for improving treatment outcomes.

Purpose of the Study:

  • To investigate the role of death receptor resistance in breast cancer progression.
  • To identify specific molecular mechanisms underlying acquired resistance to tumor necrosis factor (TNF) in breast cancer cells.

Main Methods:

  • Utilized the estrogen receptor alpha (ER)-positive MCF7 breast cancer cell line.
  • Investigated changes in estrogen receptor (ER) signaling, death receptor pathway, and epithelial to mesenchymal transition (EMT).
  • Assessed apoptosis, NF-kappaB signaling, and multi-drug resistance phenotype.

Main Results:

  • TNF resistance in MCF7 cells was linked to loss of ER expression and a multi-drug resistant phenotype.
  • Resistant cells showed altered ER signaling, reduced ER target gene expression, and blocked extrinsic apoptosis.
  • Increased NF-kappaB survival signaling and EMT were observed, contributing to a more aggressive phenotype.

Conclusions:

  • Acquired resistance to TNF involves coordinated changes in ER signaling, death receptor pathway, and EMT.
  • These alterations promote a more aggressive and chemoresistant breast cancer phenotype.
  • This study provides insights into mechanisms of acquired resistance to TNF, aiding understanding of breast cancer progression during chemotherapy.

More Related Videos

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells06:54

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

Published on: October 27, 2020

Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure09:38

Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure

Published on: August 11, 2017

Related Concept Videos

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...
Adaptive Mechanisms in Cancer Cells02:53

Adaptive Mechanisms in Cancer Cells

Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
Adaptive Mechanisms in Cancer Cells02:53

Adaptive Mechanisms in Cancer Cells

Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
Treatment Resistant Cancers02:56

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR activation may...
Metastasis02:30

Metastasis

Metastasis is the spread of cancer cells from the original site to distant locations in the body. Cancer cells can spread via blood vessels (hematogenous) as well as lymph vessels in the body.
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...