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Updated: Aug 15, 2025

A Multiplexed Luciferase-based Screening Platform for Interrogating Cancer-associated Signal Transduction in Cultured Cells
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Transcriptomic Changes Associated with ERBB2 Overexpression in Colorectal Cancer Implicate a Potential Role of the

Eman A Abdul Razzaq1,2, Khuloud Bajbouj2, Amal Bouzid1

  • 1Sharjah Institute for Medical Research, University of Sharjah, Sharjah P.O. Box 27272, United Arab Emirates.

Cancers
|January 8, 2023
PubMed

Insights

This study investigated Human Epidermal Growth Factor Receptor 2 (HER2) in colorectal cancer (CRC). Transcriptomic analysis revealed HER2 influences CRC pathogenesis via Wnt/β-catenin signaling and NKX2-5 expression, identifying potential therapeutic targets.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genomics

Background:

  • Colorectal cancer (CRC) is a leading cause of cancer mortality globally.
  • Precision medicine, guided by transcriptomic profiling, has identified targets like Human Epidermal Growth Factor Receptor 2 (HER2) in CRC.
  • Despite HER2's potential, no HER2-based treatments are approved for CRC.

Purpose of the Study:

  • To investigate the transcriptomic changes associated with HER2 overexpression in colorectal cancer.
  • To identify potential therapeutic targets co-expressed with HER2 in CRC.
  • To elucidate the role of HER2 in CRC pathogenesis through pathway analysis.

Main Methods:

  • Whole transcriptome RNA sequencing was performed on 11 HER2+ and 3 HER2- CRC patients.
  • Transcriptomic profiling was conducted on CRC cell lines and normal colon cell lines with ectopic HER2 overexpression.
  • Gene Set Enrichment Analysis (GSEA) was employed to identify enriched pathways.

Main Results:

  • Significant transcriptomic alterations were observed in HER2-overexpressing CRC cells and patients compared to controls.
  • HER2 was found to regulate CRC pathogenesis through a HER2-dependent pathway involving Wnt/β-catenin signaling.
  • This pathway impacts the expression of the homeobox gene NK2 homeobox 5 (NKX2-5).

Conclusions:

  • HER2 plays a significant role in colorectal cancer pathogenesis.
  • The Wnt/β-catenin signaling pathway, mediated by HER2, influences NKX2-5 expression in CRC.
  • This study identifies novel, co-expressed targets with HER2 in CRC, warranting further investigation for therapeutic development.
Keywords:
ERBB2HER2NKX2-5RNA-seqWnt signalingcolorectal cancerwhole transcriptomic analysis

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