Related Experiment Video

Updated: Nov 11, 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

1.2K

Autophagy inhibition perturbs ERBB2 trafficking and abolishes tumorigenesis in ERBB2-driven breast cancer

Mingang Hao1, Syn Kok Yeo1, Jun-Lin Guan1

  • 1Department of Cancer Biology, University of Cincinnati College of Medicine, Cincinnati, OH, USA.

Autophagy
|March 24, 2021
PubMed

Insights

Autophagy inhibition halts mammary tumor growth in ERBB2-driven breast cancer (BrCA) models. This study reveals a novel mechanism where autophagy promotes tumorigenesis, offering new avenues for anti-ERBB2 therapies.

Area of Science:

  • Oncology
  • Cell Biology
  • Molecular Biology

Background:

  • Autophagy modulation is a promising cancer therapy strategy.
  • The role of Rb1cc1, encompassing autophagy and non-canonical functions, in cancer is under investigation.
  • ERBB2-driven breast cancer (BrCA) presents a significant therapeutic challenge.

Purpose of the Study:

  • To genetically assess the role of Rb1cc1's autophagy and non-canonical functions in an ERBB2-driven BrCA model.
  • To elucidate the mechanistic link between autophagy and ERBB2-driven mammary tumorigenesis.
  • To explore novel therapeutic strategies targeting autophagy in ERBB2-driven BrCA.

Main Methods:

  • Utilized a novel Rb1cc1 mutant knockin mice model.
  • Employed a rigorous genetic approach to study mammary tumorigenesis.
  • Investigated the impact of autophagy abrogation on ERBB2 intracellular trafficking and release.

Main Results:

  • Autophagy abrogation significantly inhibited mammary tumorigenesis in the ERBB2-driven BrCA model.
  • The inhibitory effect was more pronounced compared to PyMT and brca1-null models.
  • Autophagy inhibition disrupted ERBB2 trafficking and promoted its release via small extracellular vesicles.

Conclusions:

  • Autophagy plays a crucial role in promoting tumorigenesis in ERBB2-driven BrCA through a novel mechanism.
  • Targeting autophagy could be a potent supplementary strategy for anti-ERBB2 therapies.
  • Understanding autophagy's non-canonical functions may reveal new therapeutic targets.
Keywords:
AutophagyERBB2-positive breast cancerFIP200/RB1CC1small extracellular vesicles

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

818
Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells06:54

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells

Published on: October 27, 2020

13.7K

Related Concept Videos

Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
7.3K
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...
4.8K
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...
4.0K
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
5.2K
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
8.1K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
4.5K