DNA strand with a ZEB1 protein, symbolizing DNA repair in cancer cells

Can This Protein Make Cancer Treatment More Effective?

Lena Kashyap in Health & Wellness December 2025 • 4 min read.

"New research highlights the potential of ZEB1 as a key player in DNA repair, offering new avenues for improving chemoresistance in colorectal cancer."

Chemo- and radio-resistance pose significant challenges in cancer treatment, often leading to recurrence and poorer outcomes. Researchers are constantly seeking ways to improve the effectiveness of these therapies and overcome resistance.

Recent studies suggest a connection between metastasis, cancer stem cells, and resistance to treatments. Epithelial-to-mesenchymal transition (EMT), where cancer cells gain migratory and invasive properties, plays a role in this resistance. Zinc finger E-box binding homeobox 1 (ZEB1) is a protein known to contribute to EMT and stemness, but its role in chemo- and radio-resistance is still being explored.

New research sheds light on how ZEB1 affects DNA repair processes in colorectal cancer cells. By understanding ZEB1's function, scientists hope to develop strategies that make cancer cells more vulnerable to treatment.

ZEB1's Role in DNA Repair: A New Target for Cancer Treatment?

DNA strand with a ZEB1 protein, symbolizing DNA repair in cancer cells

The study investigated how ZEB1 interacts with DNA damage response (DDR), the mechanisms cells use to repair damaged DNA. It was already known that ZEB1 affects the deubiquitylating activity of ubiquitin-specific peptidase (USP)7, which is important for DNA repair. Researchers hypothesized that ZEB1, as a transcriptional suppressor, might influence DDR by affecting other key components involved in DNA repair.

Using a technique called ChIP-on-chip, the researchers mapped where ZEB1 binds to DNA in colorectal cancer cells. This revealed that ZEB1 occupies regions near genes associated with DDR, specifically USP17, chromodomain helicase DNA-binding protein 1-like (CHD1L), and double homeobox 4 (DUX4).

Here's what the study found:

ZEB1 Targets DDR Genes: ZEB1 directly interacts with the genes USP17, CHD1L, and DUX4, all involved in DNA damage response.
E-boxes and ZEB1 Binding: Specific DNA sequences (E-boxes) within these genes confirm ZEB1's role as a transcriptional repressor.
Knocking Down ZEB1 Increases Gene Expression: When ZEB1 was reduced, the expression of USP17, CHD1L, and DUX4 increased, indicating ZEB1 normally suppresses these genes.
Increased Sensitivity to Chemotherapy: Reducing ZEB1 made cancer cells more sensitive to chemotherapy drugs, leading to cell cycle arrest and increased apoptosis (cell death).

These findings suggest that ZEB1 suppresses these three genes, leading to a dysregulated DDR and contributing to chemoresistance. By identifying these downstream targets, the study highlights a new mechanism by which ZEB1 promotes chemoresistance in colorectal cancer.

The Future of Cancer Treatment: Targeting ZEB1

This research provides a foundation for understanding how ZEB1 regulates DDR and contributes to chemoresistance. It suggests that inhibiting ZEB1 could be a promising strategy for improving cancer treatment.

By targeting ZEB1, researchers aim to simultaneously disrupt EMT, reduce stemness, and overcome drug resistance—three critical factors in cancer progression.

Further studies are needed to fully elucidate the detailed functions of USP17, CHD1L, and DUX4 in DDR and to develop effective ZEB1 inhibitors. However, this research offers a new avenue for developing more effective and targeted cancer therapies.

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This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.3892/or.2017.5888, Alternate LINK

Title: Potential Role Of Zeb1 As A Dna Repair Regulator In Colorectal Cancer Cells Revealed By Cancer-Associated Promoter Profiling

Subject: Cancer Research

Journal: Oncology Reports

Publisher: Spandidos Publications

Authors: Miao Wang, Su-Fei He, Lei-Lei Liu, Xiao-Xia Sun, Fan Yang, Qian Ge, Wei-Kang Wong, Jing-Yan Meng

Published: 2017-04-01

Everything You Need To Know

What role does the protein ZEB1 play in cancer treatment?

The protein, ZEB1, plays a crucial role in DNA repair mechanisms within colorectal cancer cells. Scientists have discovered that ZEB1 influences the DNA damage response (DDR), specifically by interacting with the genes USP17, CHD1L, and DUX4, which are essential for DNA repair. This interaction suggests that ZEB1 can affect how cancer cells respond to treatments.

Why is understanding the function of ZEB1 important in cancer treatment?

ZEB1's significance lies in its potential to impact how cancer cells respond to chemotherapy. Research indicates that ZEB1 contributes to chemoresistance, making cancer cells less vulnerable to treatment. The identification of ZEB1's role in regulating DDR opens new avenues for improving cancer treatment by making cancer cells more susceptible to existing therapies. By targeting ZEB1, scientists hope to enhance the effectiveness of chemotherapy and improve patient outcomes.

How is Epithelial-to-mesenchymal transition (EMT) connected to ZEB1 and cancer treatment?

Epithelial-to-mesenchymal transition (EMT) is a process where cancer cells acquire properties that make them more invasive and likely to spread to other parts of the body. ZEB1 is known to contribute to EMT and stemness, which are linked to chemoresistance. This means that by influencing EMT, ZEB1 indirectly promotes resistance to chemotherapy and radiation, making cancer more difficult to treat.

What method did scientists use to study ZEB1's interaction with DNA?

The study utilized a technique called ChIP-on-chip to map where ZEB1 binds to DNA in colorectal cancer cells. This method helped researchers identify the specific genes that ZEB1 interacts with. They found that ZEB1 directly targets genes involved in DNA damage response (DDR), including USP17, CHD1L, and DUX4. By understanding these interactions, scientists can better comprehend how ZEB1 influences cancer cell behavior and treatment outcomes.

How can targeting ZEB1 improve cancer treatment?

Inhibiting ZEB1 holds promise as a strategy to improve cancer treatment outcomes. When ZEB1's activity is reduced, cancer cells become more sensitive to chemotherapy. This increased sensitivity leads to cell cycle arrest and apoptosis (cell death), effectively killing the cancer cells. This suggests that targeting ZEB1 could enhance the effectiveness of chemotherapy and potentially improve patient survival rates.