Related Experiment Video

Updated: Aug 6, 2026

The Establishment of a Lung Colonization Assay for Circulating Tumor Cell Visualization in Lung Tissues
07:39

The Establishment of a Lung Colonization Assay for Circulating Tumor Cell Visualization in Lung Tissues

Published on: June 16, 2018

RepID orchestrates CDH1 and CTNNB1 homeostasis to regulate metastatic potential in small cell lung cancer

Dong-Kyu Kim1, Jae-Hyun Jo1, Jong-Uk Park1

  • 1Department of Biochemistry, Chungbuk National University, Cheongju, 28644, South Korea; Department of Biological Sciences and Biotechnology, Chungbuk National University, Cheongju, 28644, South Korea.

Biochemical and Biophysical Research Communications
|July 22, 2026
PubMed

Insights

Replication initiation determinant protein (RepID) suppresses small cell lung cancer (SCLC) metastasis. Loss of RepID enhances SCLC cell migration and invasion, revealing a potential therapeutic target for this aggressive cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Metastasis

Background:

  • Small cell lung cancer (SCLC) is characterized by aggressive progression and early metastasis.
  • The molecular mechanisms driving SCLC metastasis remain largely unknown.
  • Identifying novel suppressors of metastatic potential is crucial for therapeutic development.

Purpose of the Study:

  • To identify molecular drivers that suppress metastatic potential in SCLC.
  • To investigate the role of replication initiation determinant protein (RepID) in SCLC metastasis.
  • To elucidate the mechanisms by which RepID regulates SCLC cell behavior.

Main Methods:

  • Analysis of patient-derived SCLC datasets to correlate RepID expression with clinical outcomes.
  • CRISPR-Cas9-mediated gene depletion to assess the functional impact of RepID loss.
  • In vitro assays to evaluate cell morphology, migration, and invasion.
  • Mechanistic studies involving gene transcription, protein stabilization, and ubiquitination pathways (e.g., CRL4, ETS1, CDH1, CTNNB1, CUL1 neddylation).

Main Results:

  • RepID expression is significantly reduced in metastatic SCLC tumors, correlating with poor prognosis.
  • RepID deficiency induces a mesenchymal transition, increasing SCLC cell polarity, cytoskeletal rearrangement, migration, and invasion.
  • RepID maintains epithelial homeostasis by regulating CDH1 transcription via ETS1 and stabilizing CTNNB1 protein.
  • Loss of RepID leads to increased CUL1 abundance and neddylation, accelerating CTNNB1 degradation.
  • RepID-dependent proteostasis is reversible, and RepID re-expression restores adhesion and reduces invasion.

Conclusions:

  • RepID acts as a critical suppressor of SCLC metastatic potential.
  • RepID regulates SCLC metastasis through a dual mechanism involving transcriptional control of epithelial integrity and post-translational regulation of the CRL1-CTNNB1 axis.
  • RepID represents a novel molecular rheostat and a potential therapeutic vulnerability in SCLC.
Keywords:
CDH1CTNNB1EMTRepIDSCLC metastasis

Related Concept Videos

Metastasis02:30

Metastasis

Metastasis is the spread of cancer cells from the original site to distant locations in the body. Cancer cells can spread via blood vessels (hematogenous) as well as lymph vessels in the body.
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...
Cadherins in Tissue Organization01:19

Cadherins in Tissue Organization

The cadherins are a superfamily of cell adhesion molecules comprising over 180 variants, with specific tissues expressing a particular combination of cadherin types. Cadherins generally exhibit homophilic binding; i.e., cadherins on one cell bind to cadherins of the same or closely related type on another cell. Thus, cells of the same type have a specific affinity to bind to each other and sort themselves into clusters to form tissues.
Cell Sorting During Development
Cell sorting plays an...
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...
Adaptive Mechanisms in Cancer Cells02:53

Adaptive Mechanisms in Cancer Cells

Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
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 results in tumor...