Objective: Head and neck squamous cell carcinoma (HNSCC) is the most common type of malignancy in the head and neck region worldwide. The therapeutic strategies for HNSCC remain unsatisfying and limited. Here, we found a population of resistant Bmi1-expressing cells in the presence of cetuximab treatment and reported a novel role of SRY-box transcription factor 18 (SOX18), a member of the SOX family, in promoting HNSCC resistance to cetuximab. This study aimed to investigate the regulatory mechanism of Sox18 in Bmi1-positive cells and to search for better therapeutic targets.
Methods: We successfully obtained Bmi1, Rosa, and Rosa mice and identified Bmi1-expressing cells through lineage tracing. SOX18 expression in HNSCC and normal tissues was analyzed by immunohistochemistry, colocalization of Sox18, and Bmi1-expressing cells was analyzed by immunofluorescence, and SOX18 expression in SCC9 cell lines was quantified by western blotting and quantitative real-time PCR. The investigation of the mechanism of SOX18-mediated cetuximab resistance in Bmi1-positive cells was based on the analysis of single-cell RNA-seq data obtained from the Gene Expression Omnibus (GEO) database. Western blotting was performed to verify the results obtained from the single-cell RNA-seq analysis.
Results: In our study, we demonstrated that Bmi1-expressing cells were resistant to cetuximab treatment and that depletion of Bmi1-expressing cells improved cetuximab efficacy in HNSCC. We then discovered that Sox18 mediated the stem cell-like properties of Bmi1-expressing cells and promoted cellular cetuximab resistance through an oxidative phosphorylation pathway. There was a significant downregulation of key genes in the oxidative phosphorylation pathway in Sox18 knockout cell lines.
Conclusions: Taken together, the findings of our study suggest that Sox18 mediates the resistance of Bmi1-expressing cells to cetuximab in HNSCC via the oxidative phosphorylation pathway.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1111/odi.14596 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Cathepsin-facilitated invasion of BMI1-high hepatocellular carcinoma cells drives bile duct tumor thrombi formation.
Nat Commun
November 2023
Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA medicine, Sun Yat-sen Memorial Hospital, State Key Laboratory of Oncology in South China, Sun Yat-sen University, Guangzhou, 510120, China.
Bile duct tumor thrombosis (BDTT) is a complication mostly observed in patients with advanced hepatocellular carcinoma (HCC), causing jaundice and associated with poor clinical outcome. However, its underlying molecular mechanism is unclear. Here, we develop spontaneous preclinical HCC animal models with BDTT to identify the role of BMI1 expressing tumor initiating cells (BMI1 TICs) in inducing BDTT.
View Article and Find Full Text PDFSOX18 meditates the resistance of Bmi1-expressing cells to cetuximab in HNSCC.
Oral Dis
April 2024
Oncology Department, Chinese PLA General Hospital, Beijing, China.
Objective: Head and neck squamous cell carcinoma (HNSCC) is the most common type of malignancy in the head and neck region worldwide. The therapeutic strategies for HNSCC remain unsatisfying and limited. Here, we found a population of resistant Bmi1-expressing cells in the presence of cetuximab treatment and reported a novel role of SRY-box transcription factor 18 (SOX18), a member of the SOX family, in promoting HNSCC resistance to cetuximab.
View Article and Find Full Text PDFAge disparities in intestinal stem cell quantities: a possible explanation for preterm infant susceptibility to necrotizing enterocolitis.
Pediatr Surg Int
December 2022
Department of Surgery, Section of Pediatric Surgery, Indiana University School of Medicine, Indianapolis, IN, USA.
Purpose: Preterm infants are more susceptible to necrotizing enterocolitis (NEC) than term Queryinfants. This may be due to a relative paucity of Lgr5 or Bmi1-expressing intestinal stem cells (ISCs) which are responsible for promoting intestinal recovery after injury. We hypothesized that the cellular markers of Lgr5 and Bmi1, which represent the two distinct ISC populations, would be lower in younger mice compared to older mice.
View Article and Find Full Text PDFGeneration of a squamous cell carcinoma mouse model for lineage tracing of BMI1+ cancer stem cells.
STAR Protoc
June 2021
Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA 90095, USA.
BMI1-expressing cancer stem cells (CSCs) play a key role in the development, progression, therapy resistance, recurrence, and metastasis of head and neck squamous cell carcinoma (HNSCC). Here, we present a chemically-induced HNSCC mouse model, genetically and pathologically similar to human HNSCC. This protocol describes how to use genetic lineage tracing based on the Cre-loxP recombination strategy, which allows us to study the regulation and targeting of BMI1 CSCs in primary tumors and lymph node metastases.
View Article and Find Full Text PDFBmi1 Severs as a Potential Tumor-Initiating Cell Marker and Therapeutic Target in Esophageal Squamous Cell Carcinoma.
Stem Cells Int
August 2020
Center for Translational Medicine, Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510030, China.
Esophageal squamous cell carcinoma (ESCC) is a frequent malignant tumor with low 5-year overall survival. Targeting ESCC tumor-initiating cells (TICs) may provide a new research avenue to achieve better therapeutic effects of ESCC. However, the identity and characteristics of ESCC TICs remain poorly understood.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!