In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 83, No. 7_Supplement ( 2023-04-04), p. 6705-6705
Abstract:
Esophageal squamous cell carcinoma (ESCC) is a clinically challenging disease that requires a multidisciplinary approach. Unfortunately, the scarcity of ESCC genomic data hinders the understanding of ESCC biology, disease progression and rational therapy design. Circulating tumor cells (CTCs), which are shed from the primary and metastatic tumors and then circulate within the peripheral vasculature, reflect the existing tumor heterogeneity. Here, we utilized the non-biased size-based CTC enrichment strategy in combination with the real-time RT-PCR to molecularly characterize the CTCs with cancer stem cell (CSC) or mesenchymal properties in ESCC. Comprehensive data from ESCC cell lines, mouse ESCC xenograft models and clinical ESCC peripheral blood samples emphasize the importance of TWIST1 (Twist Family BHLH Transcription Factor 1) in ESCC progression. Gain-of-function and loss-of-function analyses demonstrate that TWIST1 promotes cell migration, invasion and colony formation in ESCC cells. Moreover, positive TWIST1 expression is responsible for the chemoresistance of ESCC cells to Cisplatin and is correlated with poor overall survival in ESCC patients. In addition, we show that TWIST1 promotes malignant potential, including tumor growth, invasion and chemoresistance via the TWIST1-TGFBI-ZEB1 signaling pathway in ESCC. Meanwhile, the TWIST1-TGFBI-ZEB1 signaling pathway confers immunosuppressive conditions to the tumor microenvironment, which in turn contributes to EMT to promote tumor progression. Collectively, these findings indicate that TWIST1 has a novel role in ESCC carcinogenesis by regulating tumorigenicity and cancer stem cell properties that may be useful as a prognostic monitoring biomarker and a promising therapeutic target in clinical ESCC treatment. Citation Format: Zhen Tan, Josephine Mun-Yee Ko, Valen Zhuoyou Yu, Hoi Yan Ng, Simon Law, Maria Li Lung. Molecular detection of circulating cancer cells with cancer stem cell or mesenchymal characteristics in esophageal squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6705.
Type of Medium:
Online Resource
ISSN:
1538-7445
DOI:
10.1158/1538-7445.AM2023-6705
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2023
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
