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Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

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Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
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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.
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Non-Canonical Wnt Signaling Pathways01:41

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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...
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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...
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Receptor Downregulation in MVBs01:15

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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.
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The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
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Related Experiment Video

Updated: Sep 14, 2025

Network Pharmacology Prediction and Experimental Validation of Trichosanthes-Fritillaria thunbergii Action Mechanism Against Lung Adenocarcinoma
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A Novel Tight Junction-Nuclear Receptor Signaling Pathway Regulating Cancer Progression.

Kotaro Sugimoto1,2, Hideki Chiba1

  • 1Department of Basic Pathology, Fukushima Medical University School of Medicine, Fukushima, Japan.

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|July 25, 2025
PubMed
Summary

A new pathway links cell adhesion proteins (claudins) to nuclear receptors (NRs) via Src kinases, affecting cell differentiation and cancer progression. This discovery reveals novel mechanisms in cell signaling and disease.

Keywords:
cancerclaudinsestrogennuclear receptorsretinoic acidtight junction

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Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • Nuclear receptors (NRs) are transcription factors regulating physiological processes and implicated in cancer.
  • NR activity is modulated by ligand binding and posttranslational modifications like phosphorylation.
  • Claudins (CLDNs) are cell-cell adhesion proteins.

Purpose of the Study:

  • To identify and describe a novel signaling pathway connecting claudins (CLDNs) to nuclear receptors (NRs).
  • To elucidate the mechanisms by which this CLDN-NR pathway influences epithelial differentiation and cancer progression.

Main Methods:

  • Investigation of the signaling cascade initiated by CLDN-mediated cell-cell adhesion.
  • Analysis of Src family kinase (SFK) activation.
  • Assessment of NR phosphorylation and functional consequences.

Main Results:

  • CLDN-mediated adhesion activates SFKs, leading to serine phosphorylation of NRs.
  • This novel CLDN-NR pathway is crucial for epithelial differentiation in stem cells.
  • The pathway also plays a significant role in promoting cancer progression.

Conclusions:

  • A newly discovered CLDN-NR signaling pathway provides critical insights into cell adhesion, differentiation, and cancer.
  • Understanding this pathway offers potential therapeutic targets for cancer and other diseases.