Related Experiment Video

Updated: May 14, 2025

Live Imaging to Study Microtubule Dynamic Instability in Taxane-resistant Breast Cancers
06:02

Live Imaging to Study Microtubule Dynamic Instability in Taxane-resistant Breast Cancers

Published on: February 20, 2017

7.5K

TRPM4 channels contribute to Adriamycin chemoresistance in breast cancer cells

Juan Guo1, Fang Liu2, Xinyue Yang3

  • 1Institute of Medical Research, Northwestern Polytechnical University, Xi'an, 710072, China; National Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and Toxicology, Beijing, China.

European Journal of Pharmacology
|April 18, 2025
PubMed

Insights

Transient receptor potential melastatin 4 (TRPM4) channel upregulation promotes chemoresistance in breast cancer by increasing P-glycoprotein. Targeting TRPM4 may overcome drug resistance and improve treatment outcomes.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Chemoresistance is a major obstacle in breast cancer treatment.
  • Transient receptor potential melastatin 4 (TRPM4) is implicated in cellular processes.
  • Understanding novel resistance mechanisms is crucial for therapeutic advancement.

Purpose of the Study:

  • To investigate the role of TRPM4 in doxorubicin (ADR) resistance in breast cancer.
  • To elucidate the molecular mechanisms by which TRPM4 influences chemoresistance.
  • To explore the potential of TRPM4 as a therapeutic target.

Main Methods:

  • Utilized MCF-7/ADR and MCF-7 cell lines to study TRPM4 expression and function.
  • Employed pharmacological inhibition and genetic knockdown of TRPM4.
  • Analyzed P-glycoprotein (P-gp) and NF-κB levels via Western blot.
  • Assessed cellular swelling and membrane potential changes.
  • Correlated TRPM4 expression with patient survival data from TCGA.

Main Results:

  • TRPM4 expression was significantly upregulated in ADR-resistant breast cancer cells.
  • TRPM4 inhibition or knockdown restored sensitivity to doxorubicin.
  • TRPM4 overexpression reduced sensitivity to ADR in non-resistant cells.
  • Elevated TRPM4 drives P-gp upregulation through TRPM4-mediated cellular swelling, not membrane depolarization.
  • TRPM4 inhibition suppressed NF-κB levels.
  • High TRPM4 expression correlated with reduced patient survival.

Conclusions:

  • TRPM4 plays a critical role in modulating doxorubicin resistance in breast cancer.
  • TRPM4-induced cellular swelling is a key mechanism driving P-gp overexpression.
  • Targeting TRPM4 offers a potential strategy to overcome chemoresistance and improve breast cancer therapy.
Keywords:
ADR resistanceCell swellingMCF-7P-glycoproteinTRPM4

More Related Videos

Enhancement of Apoptotic and Autophagic Induction by a Novel Synthetic C-1 Analogue of 7-deoxypancratistatin in Human Breast Adenocarcinoma and Neuroblastoma Cells with Tamoxifen19:44

Enhancement of Apoptotic and Autophagic Induction by a Novel Synthetic C-1 Analogue of 7-deoxypancratistatin in Human Breast Adenocarcinoma and Neuroblastoma Cells with Tamoxifen

Published on: May 30, 2012

18.6K
Author Spotlight: Unveiling the Role of TMOD3 in Platinum Resistance and Immune Infiltration in Ovarian Cancer09:40

Author Spotlight: Unveiling the Role of TMOD3 in Platinum Resistance and Immune Infiltration in Ovarian Cancer

Published on: August 2, 2024

2.5K

Related Concept Videos

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...
3.2K
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...
3.7K
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
7.4K
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...
4.6K
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...
2.0K
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...
6.3K