SUMOylation machinery protein, PIAS4 role in breast cancer cell proliferation and drug sensitivity

Mohammed A M Salih1,2,3, Mohamed M A E L Salem4, Muhammad Ali Shahid1

  • 1Institute of Cancer Therapeutics, University of Bradford, Bradford, UK.

Molecular Biology Reports
|January 30, 2026
PubMed
Abstract

Insights

PIAS4 protein may overcome doxorubicin resistance in breast cancer by reducing cell survival and invasiveness. This finding suggests PIAS4 as a potential therapeutic target for improving chemotherapy effectiveness.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Breast cancer presents a significant global health challenge, with doxorubicin (DOX) resistance impeding effective treatment.
  • SUMOylation, a post-translational modification, is implicated in cancer progression and therapy resistance.
  • PIAS4, a SUMO E3 ligase, is involved in genome stability and stress response, but its role in breast cancer and DOX resistance is unclear.

Purpose of the Study:

  • To investigate the role of PIAS4 in mediating doxorubicin resistance in breast cancer.
  • To explore PIAS4's function in breast cancer progression and its impact on chemoresistance.

Main Methods:

  • Quantitative PCR (qPCR) to compare SUMOylation gene expression in naked mole-rats (NMRs) and breast cancer cells (MCF-7).
  • Functional studies in MCF-7 cells overexpressing PIAS4 to assess proliferation, invasion, and drug sensitivity.
  • Western blot analysis to examine protein expression changes, including Bcl-2, after doxorubicin treatment.

Main Results:

  • PIAS4 exhibited higher expression in NMR intestinal tissue compared to MCF-7 cells.
  • Overexpression of PIAS4 in MCF-7 cells significantly reduced colony formation, invasiveness, and doxorubicin resistance.
  • Doxorubicin treatment led to downregulated Bcl-2 protein levels in PIAS4-overexpressing cells, suggesting a role in apoptosis.

Conclusions:

  • PIAS4 expression influences breast cancer cell survival, invasiveness, and chemoresistance, partly through modulation of anti-apoptotic pathways.
  • PIAS4 emerges as a potential biomarker for predicting treatment response.
  • Targeting PIAS4 could be a therapeutic strategy to overcome anthracycline resistance in breast cancer.

Related Concept Videos

Protein Translocation Machinery on the ER Membrane01:28

Protein Translocation Machinery on the ER Membrane

The translocon complex situated on the ER membrane is the main gateway for the protein secretory pathway. It facilitates the transport of nascent peptides into the ER lumen and their insertion into the ER membrane.
Sec61 protein conducting channel
In eukaryotes, the translocon complex comprises a core heterotrimeric translocator channel called the Sec61 complex. This channel includes three transmembrane proteins, Sec61α, Sec61β, and Sec61γ, and is the largest subunit of the...
6.8K
Role of Proteins in the Human Body01:28

Role of Proteins in the Human Body

Proteins are the building block of life. They are also  the most abundant macromolecules with as many diverse roles in the body. They are part of many structural components that provide unique shapes and structures to animal cells, tissues, and organs. In addition, they also act as biological catalysts and carry out several anabolic and catabolic reactions. Notably, some proteins are chemical messengers and regulate many critical processes, such as metabolism, growth, and development. They...
6.4K
Hepatic Drug Clearance: Role of Transporters01:14

Hepatic Drug Clearance: Role of Transporters

In the liver and bile canaliculi, influx and efflux transporters modification can influence intrinsic clearance. Transporters play a significant role in moving drugs within liver cells. Elaborate models, such as the Biopharmaceutical Classification System (BCS), are essential to relate transporters to drug disposition. This system categorizes drugs into four classes based on solubility and permeability, providing insights into elimination routes and the effects of transporters following oral...
309
Cells Coordinate Growth and Proliferation02:36

Cells Coordinate Growth and Proliferation

Cell size is a significant factor impacting cellular design, function, and fitness. There exists some internal coordination by which cells double their masses before division, thus, achieving homeostasis. Coordination between cell growth and proliferation depends on the checkpoints in between cell cycle phases. Loss of coordination or failure in the checkpoint mechanism can drive the cell to uncontrolled growth and loss of cellular function. Like dividing cells that coordinate cellular growth,...
5.1K
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
5.2K
Factors Affecting Protein-Drug Binding: Drug-Related Factors01:18

Factors Affecting Protein-Drug Binding: Drug-Related Factors

Drug binding to proteins is a complex phenomenon influenced by various drug-related factors, each playing a significant role in the interaction between drugs and proteins within the body.
One crucial factor in drug-protein binding is the drug's lipophilicity or its affinity for fat. More lipophilic drugs tend to have higher binding extents. For example, highly lipophilic drugs like cloxacillin exhibit substantial protein binding, with as much as 95% of the drug binding to proteins. In...
482