Digital illustration of ErbB3 protein being degraded inside a cell.

ErbB3's Fate: How Cells Control a Key Cancer Player

Mira Elwood in Science & Nature December 2025 • 4 min read.

"Unraveling the mechanisms behind ErbB3 degradation could unlock new strategies for cancer treatment."

ErbB3, a protein that is of the the epidermal growth factor receptor (EGFR) family, plays a significant role in cell growth and survival. While ErbB3 has been known as one of the feable kinase proteins, its ability to interact with other proteins makes it a vital component in proliferative signaling. Like other proteins, cells have mechanisms to control ErbB3 levels, ensuring proper function and preventing overactivity, which can cause cancer.

New research sheds light on how cells manage ErbB3 levels through a process called endocytosis, where the protein is sorted for recycling or degradation. This study dives deep into the mechanisms that control ErbB3's lifespan, specifically how it interacts with other proteins and cellular structures to decide its fate.

This article explores the processes of how ErbB3 interacts with Hrs, a key player in protein sorting, guiding ErbB3 to lysosomes—cellular recycling centers—for degradation. Understanding these interactions opens new paths for cancer treatments by manipulating protein degradation.

ErbB3's Journey: From Cell Surface to Degradation

Digital illustration of ErbB3 protein being degraded inside a cell.

The study reveals that ErbB3's journey starts with endocytosis, a process where the cell membrane folds inward to engulf the protein. Whether or not a signaling molecule called heregulin is present, ErbB3 is internalized through clathrin-mediated endocytosis. The study also pinpoints that proteasomes and lysosomes which serve as cellular clean up and recyling crew, work to regulate ErbB3 quantities.

While proteasomes manage the steady-state levels of ErbB3 within the cell, internalization events are a trigger that routes ErbB3 towards lysosomal degradation. This process involves a critical interaction between ErbB3 and Hrs, a protein that sorts other proteins into pathways that are destined to be degraded or recycled. Here's a breakdown of key steps:

Clathrin-mediated Endocytosis: ErbB3 is internalized through this pathway whether or not heregulin is present.
Hrs Interaction: ErbB3 interacts with Hrs, directing it towards late endosomes and lysosomes.
ESCRT Involvement: The ESCRT machinery facilitates the sorting of ErbB3 to lysosomes for degradation.

The study also found that when the ESCRT machinery is impaired, ErbB3 accumulates in endosomes. This emphasizes the importance of the ESCRT pathway in managing ErbB3 levels and preventing its accumulation, which could otherwise lead to unchecked signaling and cancer progression.

Targeting ErbB3: Implications for Cancer Therapy

Understanding how cells regulate ErbB3 offers opportunities for developing new cancer therapies. By targeting the interactions and pathways involved in ErbB3 degradation, treatments can be designed to reduce ErbB3 levels and inhibit its cancer-promoting effects.

Future research could focus on developing drugs that enhance the interaction between ErbB3 and Hrs, promoting its degradation. Another strategy is to target the ESCRT machinery to ensure efficient sorting of ErbB3 to lysosomes.

These findings underscore the importance of protein degradation in cancer biology and highlight the potential of targeting these processes for therapeutic intervention. By continuing to explore these mechanisms, scientists can unlock more effective cancer treatments and improve patient outcomes.

About this Article -

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This article is based on research published under:

DOI-LINK: 10.1016/j.bbamcr.2017.08.011, Alternate LINK

Title: Erbb3 Interacts With Hrs And Is Sorted To Lysosomes For Degradation

Subject: Cell Biology

Journal: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

Publisher: Elsevier BV

Authors: Anne Marthe Fosdahl, Markus Dietrich, Kay Oliver Schink, Muhammad Salman Malik, Marianne Skeie, Vibeke Bertelsen, Espen Stang

Published: 2017-12-01

Everything You Need To Know

What is ErbB3 and why is it important?

ErbB3 is a protein belonging to the epidermal growth factor receptor (EGFR) family. It plays a crucial role in cell growth and survival. It interacts with other proteins to facilitate signaling, making it a key player in cellular processes. The levels of ErbB3 are tightly controlled by the cell to prevent overactivity, which could lead to cancer.

How does the cell control ErbB3 levels?

The cell manages ErbB3 levels through a process called endocytosis. This is where the cell membrane engulfs the protein, sorting ErbB3 for either recycling or degradation. This process, whether or not signaling molecule heregulin is present, directs ErbB3 towards lysosomes. This ensures proper cellular function and prevents ErbB3 from causing uncontrolled cell growth.

What is the role of Hrs in the regulation of ErbB3?

Hrs is a protein involved in protein sorting. It interacts with ErbB3 and directs it to late endosomes and eventually to lysosomes for degradation. Without the interaction between ErbB3 and Hrs, ErbB3 might not be properly routed for degradation, potentially leading to its accumulation and contributing to cancer development. This interaction is a critical step in regulating ErbB3 levels.

What is the significance of the ESCRT machinery in relation to ErbB3?

The ESCRT machinery is essential for the proper degradation of ErbB3. It facilitates the sorting of ErbB3 to lysosomes. If the ESCRT machinery is impaired, ErbB3 accumulates in endosomes, which can lead to its over-accumulation and unchecked signaling. This directly connects to the potential for cancer progression by allowing ErbB3 to promote uncontrolled cell growth.

How does understanding ErbB3 regulation relate to cancer therapy?

Understanding the mechanisms of ErbB3 regulation opens new avenues for cancer therapy. By targeting the interactions and pathways involved in ErbB3 degradation, such as the interaction with Hrs or the function of the ESCRT machinery, treatments can be developed to reduce ErbB3 levels. This, in turn, could inhibit the cancer-promoting effects of ErbB3, offering a potential therapeutic strategy to combat cancer.