We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
FANCD2 Confers a Malignant Phenotype in Esophageal Squamous Cell Carcinoma by Regulating Cell Cycle Progression.
- Authors
Lei, Lisa Chan; Yu, Valen Zhuoyou; Ko, Josephine Mun Yee; Ning, Lvwen; Lung, Maria Li
- Abstract
Simple Summary: Fanconi anemia patients with germline FANCD2 defects are susceptible to cancers. In order to understand FANCD2 function in esophageal cancers, we used cell line, animal model, and sequencing approaches. We knocked out the FANCD2 gene and examined the functional impact of its loss on tumor growth and metastasis and performed assays for cell growth, cell cycle, and cellular localization. FANCD2 promotes tumorigenesis in this cancer. FANCD2 is significantly upregulated in tumors. Depletion of FANCD2 protein expression significantly suppresses the cancer cell proliferation and tumor colony formation and metastasis potential, as well as cell cycle progression, by involving specific cell signaling pathways. FANCD2 is moved out of the nucleus to the cytoplasm during cell cycle progression. We provide evidence of a novel role of FANCD2 in esophageal cancer progression and its potential value as a biomarker for disease management. Fanconi anemia patients with germline genetic defects in FANCD2 are highly susceptible to cancers. Esophageal squamous cell carcinoma (ESCC) is a deadly cancer. Little is known about the function of FANCD2 in ESCC. For detailed molecular and mechanistic insights on the functional role of FANCD2 in ESCC, in vivo and in vitro assays and RNA sequencing approaches were used. Utilizing Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR) technology, FANCD2 knockout models were established to examine the functional impact in mouse models for tumor growth and metastasis and in vitro assays for cell growth, cell cycle, and cellular localization. Our RNA sequence analyses were integrated with public datasets. FANCD2 confers a malignant phenotype in ESCC. FANCD2 is significantly upregulated in ESCC tumors, as compared to normal counterparts. Depletion of FANCD2 protein expression significantly suppresses the cancer cell proliferation and tumor colony formation and metastasis potential, as well as cell cycle progression, by involving cyclin-CDK and ATR/ATM signaling. FANCD2 translocates from the nucleus to the cytoplasm during cell cycle progression. We provide evidence of a novel role of FANCD2 in ESCC tumor progression and its potential usefulness as a biomarker for ESCC disease management.
- Subjects
CELL proliferation; BIOMARKERS; CELL cycle; CELL lines; CELLULAR signal transduction; CYTOPLASM; ESOPHAGEAL tumors; GENE expression; RNA; SQUAMOUS cell carcinoma; PHENOTYPES; SEQUENCE analysis
- Publication
Cancers, 2020, Vol 12, Issue 9, p2545
- ISSN
2072-6694
- Publication type
Article
- DOI
10.3390/cancers12092545