Related Experiment Video

Updated: Jun 10, 2025

Author Spotlight: A Selective Luciferase-Based Assay for Monitoring ATG4B 27 Activity in Cells
09:51

Author Spotlight: A Selective Luciferase-Based Assay for Monitoring ATG4B 27 Activity in Cells

Published on: June 30, 2023

763

Chaperone-mediated autophagy modulates Snail protein stability: implications for breast cancer metastasis

Ki-Jun Ryu1, Ki Won Lee1, Seung-Ho Park2

  • 1Division of Applied Life Science (Brain Korea 21 Four), Research Institute of Life Sciences, Gyeongsang National University, Jinju, 52828, Korea.

Molecular Cancer
|October 10, 2024
PubMed

Insights

Chaperone-mediated autophagy (CMA) degrades Snail, a protein driving breast cancer spread. In triple-negative breast cancer (TNBC), Snail evades CMA, promoting malignancy and offering a potential therapeutic target.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Biology

Background:

  • Breast cancer, particularly triple-negative breast cancer (TNBC), presents a significant clinical challenge due to its aggressive nature and poor prognosis.
  • Epithelial-mesenchymal transition (EMT) is a critical process in tumor progression, facilitating the transition from non-invasive to invasive malignancy.
  • The Snail protein is a key regulator of EMT and is typically controlled through proteasomal degradation.

Purpose of the Study:

  • To investigate a novel pathway for Snail degradation independent of the proteasome.
  • To elucidate the role of chaperone-mediated autophagy (CMA) in regulating Snail levels and its impact on breast cancer subtypes.
  • To identify potential therapeutic strategies targeting Snail regulation in breast cancer.

Main Methods:

  • Investigated Snail degradation pathways in luminal-type and triple-negative breast cancer (TNBC) cells.
  • Utilized techniques to study protein-chaperone interactions (HSC70) and lysosomal targeting.
  • Examined the effects of starvation-induced CMA activation on Snail localization and protein levels.
  • Assessed the impact of CMA-mediated Snail degradation on EMT and metastatic potential.

Main Results:

  • Identified a novel proteasome-independent pathway for Snail degradation involving chaperone-mediated autophagy (CMA), HSC70, and lysosomal targeting in luminal-type breast cancer cells.
  • Demonstrated that Snail predominantly localizes to the nucleus in TNBC cells, evading CMA-mediated degradation.
  • Showed that starvation-induced CMA activation promotes cytoplasmic translocation of Snail in TNBC cells, leading to its downregulation.
  • Found that evasion of CMA-mediated Snail degradation enhances EMT and metastatic potential in luminal-type breast cancer cells.

Conclusions:

  • Chaperone-mediated autophagy (CMA) plays a previously unrecognized role in regulating Snail degradation.
  • Dysregulation of CMA-mediated Snail degradation contributes to the aggressive phenotype and metastatic potential of breast cancer, particularly TNBC.
  • Targeting CMA-mediated Snail degradation presents a potential therapeutic strategy for breast cancer intervention.
Keywords:
Breast cancerChaperone-mediated autophagyEMTMetastasisSnail

More Related Videos

Exploring the Regulation of Lipid Droplet Catabolism through Lipophagy07:20

Exploring the Regulation of Lipid Droplet Catabolism through Lipophagy

Published on: January 31, 2025

417
siRNA Electroporation to Modulate Autophagy in Herpes Simplex Virus Type 1-Infected Monocyte-Derived Dendritic Cells09:10

siRNA Electroporation to Modulate Autophagy in Herpes Simplex Virus Type 1-Infected Monocyte-Derived Dendritic Cells

Published on: October 28, 2019

7.2K

Related Concept Videos

Regulation of Nuclear Protein Sorting01:45

Regulation of Nuclear Protein Sorting

Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
2.4K
Delivery Pathways to the Lysosome01:36

Delivery Pathways to the Lysosome

Eukaryotic cells use different mechanisms to eliminate toxic waste obsolete and worn-out substances. Lysosomes play a pivotal role in this, and hence, these substances are carried to the lysosome from other parts of the cell and extracellular space through different pathways. The most elaborately studied pathways to the lysosome are the endocytic pathways.
Endocytosis
In endocytosis, the cell membrane takes up macromolecules and particles from the surrounding medium. Clathrin-mediated...
6.2K
Autophagy01:27

Autophagy

Autophagy is a self-digesting process by which a cell protects itself from threats both within and outside the cell, ranging from abnormal proteins to invading bacteria. In this process, obsolete components of the cell and invading microbes are degraded by hydrolytic enzymes active in an acidic environment of the lysosomal lumen.
An autophagic pathway consists of a series of signaling events activated in response to diverse stress and physiological conditions such as food deprivation,...
4.2K
Destabilization of Microtubules01:45

Destabilization of Microtubules

The destabilization of microtubules can occur during different stages of the microtubule lifecycle, such as nucleation or elongation. It can take place at either end of the microtubule or in the microtubule lattices as a whole. The lifespan of individual microtubules within a cell varies according to the cell type and stage of the cell cycle. During interphase, the lifespan of the microtubule is about 30 minutes, while during cell division, it is about 15 minutes. In axonal microtubules of...
2.6K
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...
3.8K
The Spindle Assembly Checkpoint02:19

The Spindle Assembly Checkpoint

The spindle assembly checkpoint is a molecular surveillance mechanism ensuring the fidelity of chromosome segregation during anaphase. The checkpoint monitors the completion of all the prerequisite steps before chromosome segregation to determine whether the segregation process should proceed or be delayed.
Many proteins function together to control the spindle assembly checkpoint. Mutations affecting these proteins may allow cells to proceed into anaphase prematurely, resulting in the...
3.1K