ECT2+ cell group acts as cancer stem cell in malignant pleomorphic adenoma

Abstract Salivary carcinoma ex pleomorphic adenoma (CXPA) is a carcinoma that develops from benign pleomorphic adenoma, and it is characterized by aggressiveness and poor prognosis. Recent advancements in cancer stem cell (CSC) research have identified CSCs as critical contributors to tumor carcinog...

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Main Authors: Wanling Chen, Yang Wang, Zhengduo Yao, Ting Gu, Yuhua Hu, Nannan Leng, Chunye Zhang, Zhen Tian, Jiang Li
Format: Article
Language:English
Published: Nature Portfolio 2025-06-01
Series:npj Precision Oncology
Online Access:https://doi.org/10.1038/s41698-025-00974-x
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author Wanling Chen
Yang Wang
Zhengduo Yao
Ting Gu
Yuhua Hu
Nannan Leng
Chunye Zhang
Zhen Tian
Jiang Li
author_facet Wanling Chen
Yang Wang
Zhengduo Yao
Ting Gu
Yuhua Hu
Nannan Leng
Chunye Zhang
Zhen Tian
Jiang Li
author_sort Wanling Chen
collection DOAJ
description Abstract Salivary carcinoma ex pleomorphic adenoma (CXPA) is a carcinoma that develops from benign pleomorphic adenoma, and it is characterized by aggressiveness and poor prognosis. Recent advancements in cancer stem cell (CSC) research have identified CSCs as critical contributors to tumor carcinogenesis due to their unlimited self-renewal ability. Single-cell RNA sequencing has enabled a comprehensive analysis of CSC heterogeneity. However, CSCs in CXPA remain largely unexplored. In this study, we constructed a comprehensive atlas of CXPA at single-cell resolution and demonstrated that CXPA exhibited intratumoral heterogeneity. We identified four tumor epithelial cell subgroups characterized by epithelial development, cell cycle, extracellular matrix remodeling, and salivary secretion signatures. ECT2+ tumor cells in the cell cycle cluster were identified as CSCs in CXPA. Analysis of tumor tissues from patients with CXPA revealed that ECT2 expression was strongly associated with invasiveness and prognosis. Targeting the ECT2 gene significantly inhibited tumor sphere formation and aggressiveness in CXPA cell lines. Our findings provide new insights into CXPA diversity and origin, with substantial clinical implications for targeting the ECT2 gene in CXPA treatment.
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publishDate 2025-06-01
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spelling doaj-art-4964dbfc74c94d50a3f31105a11b2a122025-08-20T03:47:24ZengNature Portfolionpj Precision Oncology2397-768X2025-06-019111210.1038/s41698-025-00974-xECT2+ cell group acts as cancer stem cell in malignant pleomorphic adenomaWanling Chen0Yang Wang1Zhengduo Yao2Ting Gu3Yuhua Hu4Nannan Leng5Chunye Zhang6Zhen Tian7Jiang Li8Department of Oral Pathology, Ninth People’s Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Stomatology, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese MedicineDepartment of Oral Pathology, Ninth People’s Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Oral Pathology, Ninth People’s Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Oral Pathology, Ninth People’s Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Oral Pathology, Ninth People’s Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Oral Pathology, Ninth People’s Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Oral Pathology, Ninth People’s Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Oral Pathology, Ninth People’s Hospital, Shanghai Jiao Tong University School of MedicineAbstract Salivary carcinoma ex pleomorphic adenoma (CXPA) is a carcinoma that develops from benign pleomorphic adenoma, and it is characterized by aggressiveness and poor prognosis. Recent advancements in cancer stem cell (CSC) research have identified CSCs as critical contributors to tumor carcinogenesis due to their unlimited self-renewal ability. Single-cell RNA sequencing has enabled a comprehensive analysis of CSC heterogeneity. However, CSCs in CXPA remain largely unexplored. In this study, we constructed a comprehensive atlas of CXPA at single-cell resolution and demonstrated that CXPA exhibited intratumoral heterogeneity. We identified four tumor epithelial cell subgroups characterized by epithelial development, cell cycle, extracellular matrix remodeling, and salivary secretion signatures. ECT2+ tumor cells in the cell cycle cluster were identified as CSCs in CXPA. Analysis of tumor tissues from patients with CXPA revealed that ECT2 expression was strongly associated with invasiveness and prognosis. Targeting the ECT2 gene significantly inhibited tumor sphere formation and aggressiveness in CXPA cell lines. Our findings provide new insights into CXPA diversity and origin, with substantial clinical implications for targeting the ECT2 gene in CXPA treatment.https://doi.org/10.1038/s41698-025-00974-x
spellingShingle Wanling Chen
Yang Wang
Zhengduo Yao
Ting Gu
Yuhua Hu
Nannan Leng
Chunye Zhang
Zhen Tian
Jiang Li
ECT2+ cell group acts as cancer stem cell in malignant pleomorphic adenoma
npj Precision Oncology
title ECT2+ cell group acts as cancer stem cell in malignant pleomorphic adenoma
title_full ECT2+ cell group acts as cancer stem cell in malignant pleomorphic adenoma
title_fullStr ECT2+ cell group acts as cancer stem cell in malignant pleomorphic adenoma
title_full_unstemmed ECT2+ cell group acts as cancer stem cell in malignant pleomorphic adenoma
title_short ECT2+ cell group acts as cancer stem cell in malignant pleomorphic adenoma
title_sort ect2 cell group acts as cancer stem cell in malignant pleomorphic adenoma
url https://doi.org/10.1038/s41698-025-00974-x
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