Concurrent Wnt pathway component expression in breast and colorectal cancer

Maria Michelli1, Alexandros Zougros1, Ilenia Chatziandreou1

  • 1First Department of Pathology, Medical School, National and Kapodistrian University of Athens, Mikras Asias 75, Goudi, Athens, Greece.

Insights

Wnt pathway gene expression in breast and colorectal cancers shows distinct patterns. Understanding these Wnt signaling variations is crucial for effective patient selection for Wnt pathway inhibitor therapies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • The Wnt signaling pathway is vital for cell functions and often dysregulated in breast and colorectal cancers.
  • This pathway is a key therapeutic target, with numerous drugs in clinical trials.

Purpose of the Study:

  • To analyze Wnt pathway component mRNA expression (Wnt3, Frizzled 7, LEF1) in breast and colorectal carcinomas.
  • To investigate concurrent expression patterns and correlations with clinicopathological features.

Main Methods:

  • Quantitative analysis of Wnt3, Frizzled 7 (FZD7), and LEF1 mRNA expression levels in 82 breast and 102 colorectal tumors.
  • Correlation analysis between gene expression levels and clinicopathological parameters.

Main Results:

  • Breast cancer: Increased WNT3 (54%), decreased FZD7 (82%), decreased LEF1 (43%). WNT3 correlated with tumor grade (p=0.021).
  • Colorectal cancer: Increased WNT3 (60%), FZD7 (37%), LEF1 (48%). LEF1 correlated with pT-category (p=0.027).
  • Significant WNT3/LEF1 and FZD7/LEF1 correlations found in both cancer types.

Conclusions:

  • Wnt pathway gene expression has potential clinical significance in breast and colorectal cancers.
  • Distinct expression patterns highlight pathway complexity in carcinogenesis.
  • Patient selection is essential for Wnt pathway inhibitor efficacy.

Related Concept Videos

Canonical Wnt Signaling Pathway02:54

Canonical Wnt Signaling Pathway

The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which...
10.2K
Non-Canonical Wnt Signaling Pathways01:41

Non-Canonical Wnt Signaling Pathways

Wnt is a zygotic effect gene that is expressed during very early embryonic development. It regulates various processes in animals starting from early development through the adult stage, such as organogenesis in the embryo and maintenance of neuronal and blood stem cells. Wnt proteins can induce a wide variety of intracellular pathways depending upon the specific abilities of different Wnt ligands to form a complex with shared and cognate receptors in the presence of different co-receptors. The...
8.1K
Tumor Progression02:07

Tumor Progression

Tumor progression is a phenomenon where the pre-formed tumor acquires successive mutations to become clinically more aggressive and malignant. In the 1950s, Foulds first described the stepwise progression of cancer cells through successive stages.
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
7.1K
Role Of Notch Signalling In Intestinal Stem Cell Renewal01:12

Role Of Notch Signalling In Intestinal Stem Cell Renewal

Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
2.3K
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
7.1K
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...
4.5K