CRISPR/Cas9 Screening Highlights PFKFB3 Gene as a Major Contributor to 5-Fluorouracil Resistance in Esophageal Cancer

Xuefeng F, Yang H, Xu P, Zhang S, Britzen-Laurent N, Bao L, Grützmann R, Krautz C, Pilarsky C (2025)

Publication Language: English

Publication Type: Journal article

Publication year: 2025

Journal

Cancers MDPI

Book Volume: 17

Article Number: 1637

Journal Issue: 10

DOI: 10.3390/cancers17101637

Abstract

Background: Esophageal cancer (EC) is the eighth most common cancer and the sixth most common cause of death worldwide. Esophageal squamous cell carcinoma (ESCC) comprises the majority of esophageal cancers globally, and 5-Fluorouraci (5-FU) is one of the commonly used chemotherapeutics for this type of cancer. Chemoresistance to drugs is a main obstacle in the successful treatment of this malignancy. Methods: In this study, we used the CRISPR/Cas9 screening method to determine the target gene related to 5-FU drug resistance in esophageal cancer. Results: Our research findings indicate that the loss of PFKFB3 can increase the resistance of different human esophageal squamous cell carcinoma cell lines to 5-FU through various pathways. Specifically, in KYSE-70 cells, loss of PFKFB3 can induce epithelial–mesenchymal transition (EMT) and prolong the S phase of the cell cycle, allowing cancer cells to evade the effects of 5-FU and develop resistance. In the KYSE-270 and KYSE-150 cell lines, loss of PFKFB3 can upregulate the expression of Slug and Mcl-1, indirectly regulate Chk1 and promote its autophosphorylation, which in turn inhibits apoptosis, thus counteracting the effects of 5-FU. Conclusions: Our research not only enriches our understanding of the biological characteristics of different ESCC cell lines but also provides new clinical insights for future personalized treatments. Assessing the status of PFKFB3 can help predict resistance to 5-FU in ESCC patients with different genetic backgrounds, allowing for more precise treatment planning. This personalized approach has the potential to improve treatment efficacy, reduce unnecessary drug use and side effects, and ultimately improve patient survival rates and quality of life.

Authors with CRIS profile

Pengyan Xu Professur für Chirurgische Forschung Shuman Zhang Professur für Chirurgische Forschung Nathalie Britzen-Laurent Department of Surgery Lili Bao Professur für Molekulare Gastroenterologie Robert Grützmann Lehrstuhl für Allgemein- und Viszeralchirurgie Christian Krautz Department of Surgery Christian Pilarsky Professur für Chirurgische Forschung

Involved external institutions

Juraklinik Scheßlitz DE Germany (DE)

How to cite

APA:

Xuefeng, F., Yang, H., Xu, P., Zhang, S., Britzen-Laurent, N., Bao, L.,... Pilarsky, C. (2025). CRISPR/Cas9 Screening Highlights PFKFB3 Gene as a Major Contributor to 5-Fluorouracil Resistance in Esophageal Cancer. Cancers, 17(10). https://doi.org/10.3390/cancers17101637

MLA:

Xuefeng, Feng, et al. "CRISPR/Cas9 Screening Highlights PFKFB3 Gene as a Major Contributor to 5-Fluorouracil Resistance in Esophageal Cancer." Cancers 17.10 (2025).

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