Related Experiment Video

Updated: Jun 22, 2026

Exploring the Regulation of Lipid Droplet Catabolism through Lipophagy
07:20

Exploring the Regulation of Lipid Droplet Catabolism through Lipophagy

Published on: January 31, 2025

Autophagy suppresses tumorigenesis through elimination of p62

Robin Mathew1, Cristina M Karp, Brian Beaudoin

  • 1University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA.

Cell
|June 16, 2009
PubMed

Insights

Autophagy defects in cancer cells lead to the accumulation of p62/SQSTM1 (p62), causing oxidative stress and promoting tumor growth. Restoring p62 regulation is crucial for understanding cancer development and potential therapies.

Area of Science:

  • Cellular Biology
  • Oncology
  • Molecular Biology

Background:

  • Autophagy is a cellular process involved in degrading damaged components.
  • Loss of the autophagy gene beclin1 is linked to cancer development.
  • Tumor cells use autophagy to survive stress, but defects can paradoxically promote cancer.

Purpose of the Study:

  • To investigate the role of autophagy defects in tumor progression.
  • To understand how autophagy deficiency leads to the accumulation of specific proteins and cellular damage.
  • To explore the link between p62/SQSTM1 accumulation and tumorigenesis.

Main Methods:

  • Analysis of autophagy-defective tumor cells.
  • Assessment of accumulated cellular components including p62/SQSTM1, ER chaperones, damaged mitochondria, and reactive oxygen species (ROS).
  • Investigating the impact of ROS and p62 suppression on autophagy-defect-induced damage.

Main Results:

  • Autophagy-defective tumor cells accumulate p62/SQSTM1, ER chaperones, damaged mitochondria, ROS, and show genome damage.
  • Suppression of ROS or p62 prevented damage caused by autophagy defects, indicating p62 dysregulation drives oxidative stress.
  • Sustained p62 expression altered NF-kappaB signaling and gene expression, promoting tumorigenesis.

Conclusions:

  • Defective autophagy leads to p62/SQSTM1 upregulation in tumors, contributing to cancer progression.
  • p62/SQSTM1 accumulation due to autophagy defects perturbs critical signaling pathways, driving oncogenesis.
  • Targeting p62 regulation may offer therapeutic strategies for cancers with autophagy defects.

More Related Videos

Cell-Based Drug Screening for Inhibitors of Autophagy Related 4B Cysteine Peptidase09:51

Cell-Based Drug Screening for Inhibitors of Autophagy Related 4B Cysteine Peptidase

Published on: June 30, 2023

Assessing Autophagic Flux by Measuring LC3, p62, and LAMP1 Co-localization Using Multispectral Imaging Flow Cytometry11:39

Assessing Autophagic Flux by Measuring LC3, p62, and LAMP1 Co-localization Using Multispectral Imaging Flow Cytometry

Published on: July 21, 2017

Related Concept Videos

Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
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,...
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...
Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-Critical Genes II: Tumor Suppressor Genes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-Critical Genes II: Tumor Suppressor Genes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
Loss of Tumor Suppressor Gene Functions01:12

Loss of Tumor Suppressor Gene Functions

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...