Related Experiment Video

Updated: Jun 4, 2026

An Immunofluorescent Method for Characterization of Barrett’s Esophagus Cells
08:54

An Immunofluorescent Method for Characterization of Barrett’s Esophagus Cells

Published on: July 20, 2014

Slit-Robo signaling induces malignant transformation through Hakai-mediated E-cadherin degradation during colorectal

Wei-Jie Zhou1, Zhen H Geng, Shan Chi

  • 1Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.

Cell Research
|February 2, 2011
PubMed

Insights

Slit2 and Robo1 binding triggers colorectal cancer progression by degrading E-cadherin via Hakai, promoting metastasis. Blocking this interaction inhibits tumor growth and improves survival.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Oncology

Background:

  • The Slit-Roundabout (Robo) signaling pathway regulates cell migration.
  • Epithelial-mesenchymal transition (EMT) is crucial for cancer metastasis.
  • E-cadherin (E-cad) is a key cell adhesion molecule often downregulated during EMT.

Purpose of the Study:

  • To investigate the role of Slit2 and Robo1 in colorectal cancer progression.
  • To elucidate the molecular mechanisms linking Slit2-Robo1 signaling to EMT and metastasis.
  • To assess the clinical relevance of Slit2 and Robo1 expression in colorectal carcinoma patients.

Main Methods:

  • Ectopic expression and knockdown of Slit2 and Robo1 in colorectal cancer cells.
  • Treatment with recombinant Slit2 and blockade of Slit2-Robo1 binding.
  • Assessment of E-cadherin ubiquitination and lysosomal degradation.
  • Analysis of EMT markers, tumor growth, and liver metastasis.
  • Correlation analysis of Slit2 and Robo1 expression with patient survival data.

Main Results:

  • Ectopic Slit2/Robo1 or Slit2 treatment induced E-cad ubiquitination and degradation by recruiting Hakai, promoting EMT, tumor growth, and liver metastasis.
  • Hakai knockdown rescued these effects.
  • Robo1 knockdown or blockade of Slit2-Robo1 interaction inhibited E-cad degradation and reversed EMT, reducing metastasis.
  • Ectopic Robo1 expression induced malignant transformation in HEK293 cells.
  • High Slit2 and Robo1 expression correlated with increased metastatic risk and poorer survival in colorectal cancer patients.

Conclusions:

  • Slit2-Robo1 engagement induces colorectal cancer cell carcinogenesis and metastasis.
  • This process involves Hakai-mediated E-cadherin ubiquitination and lysosomal degradation.
  • Slit2 and Robo1 serve as potential biomarkers for metastatic risk and prognosis in colorectal carcinoma.

More Related Videos

Induction of Mesenchymal-Epithelial Transitions in Sarcoma Cells11:42

Induction of Mesenchymal-Epithelial Transitions in Sarcoma Cells

Published on: April 7, 2017

Induction and Analysis of Epithelial to Mesenchymal Transition10:37

Induction and Analysis of Epithelial to Mesenchymal Transition

Published on: August 27, 2013

Related Concept Videos

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...
Hedgehog Signaling Pathway02:33

Hedgehog Signaling Pathway

The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
Hedgehog Signaling Pathway02:33

Hedgehog Signaling Pathway

The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
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...
The Ras Gene02:38

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a superfamily...
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...