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Molecular crossroads: identifying MAPK proteins bridging SMAD and dopamine pathways in breast cancer

Przemysław Borawski1,2, Tomasz Sirek2,3,4, Agata Sirek2

  • 1Independent Researcher, Włocławek, Poland.

Cell Cycle (Georgetown, Tex.)
|August 28, 2025
PubMed

Insights

This study reveals key molecular links between MAPK, SMAD, and dopamine pathways in breast cancer, identifying potential therapeutic targets. Researchers found specific genes and microRNAs that bridge these signaling cascades, offering new avenues for treatment.

Area of Science:

  • Molecular Biology
  • Oncology
  • Biochemistry

Background:

  • The transforming growth factor-beta (TGF-β)/SMAD signaling pathway, mitogen-activated protein kinase (MAPK) signaling cascade, and dopamine receptor activity are recognized contributors to tumor progression.
  • Understanding the molecular interplay between these pathways is crucial for deciphering breast cancer pathogenesis.

Purpose of the Study:

  • To investigate the molecular interactions among TGF-β/SMAD, MAPK, and dopamine signaling pathways in breast cancer.
  • To identify specific MAPK proteins that act as bridges between SMAD and dopamine signaling.
  • To discover potential biomarkers and therapeutic targets for breast cancer based on these molecular intersections.

Main Methods:

  • Transcriptomic profiling using microarrays on 405 breast cancer patients across molecular subtypes.
  • Bioinformatics-based network analysis to identify differentially expressed genes.
  • Validation of key transcripts using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and protein expression analysis via enzyme-linked immunosorbent assay (ELISA).
  • Analysis of microRNA (miRNA) regulatory interactions.

Main Results:

  • 167 differentially expressed genes were identified, with 14 consistently altered across all subtypes, including upregulated CDC42, KRAS, and TGFB1, and downregulated FGF2, FGF7, and IGF1.
  • miRNA analysis implicated miR-221, miR-222, and miR-16-5p as key regulators.
  • ELISA confirmed reduced KIT, IGF1, and FGF family proteins, and significantly upregulated KRAS protein expression in tumor tissues.
  • Protein interaction analysis highlighted key hubs connecting MAPK, SMAD, and dopamine signaling.

Conclusions:

  • This study elucidates critical molecular intersections between MAPK, SMAD, and dopamine pathways in breast cancer.
  • Identified molecular players, including specific genes and miRNAs, represent potential biomarkers and therapeutic targets for breast cancer treatment.
Keywords:
Mitogen-Activated Protein Kinase (MAPK) signalingSuppressor of Mothers Against Decapentaplegic (SMAD) pathwaybreast cancergene expressionmicroarray

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