ANGPTL1 attenuates cancer migration, invasion, and stemness through regulating FOXO3a-mediated SOX2 expression in colorectal cancer.

Autor:	Chang TY; Graduate Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan., Lan KC; Department of Emergency Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan., Chiu CY; Center of Consultation, Center for Drug Evaluation, Taipei, Taiwan., Sheu ML; Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan.; Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan., Liu SH; Graduate Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan.; Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan.; Department of Pediatrics, College of Medicine, National Taiwan University & Hospital, Taipei, Taiwan.
Jazyk:	angličtina
Zdroj:	Clinical science (London, England : 1979) [Clin Sci (Lond)] 2022 May 13; Vol. 136 (9), pp. 657-673.
DOI:	10.1042/CS20220043
Abstrakt:	Angiopoietin-like protein 1 (ANGPTL1) is a member of the ANGPTL family that suppresses angiogenesis, cancer invasion, metastasis, and cancer progression. ANGPTL1 is down-regulated in various cancers including colorectal cancer (CRC); however, the effects and mechanisms of ANGPTL1 on liver metastasis and cancer stemness in CRC are poorly understood. In the present study, we identified that ANGPTL1 was down-regulated in CRC and inversely correlated with metastasis and poor clinical outcomes in CRC patients form the ONCOMINE database and Human Tissue Microarray staining. ANGPTL1 significantly suppressed the migration/invasion abilities, the expression of cancer stem cell (CSC) markers, and sphere formation by enhancing FOXO3a expression, which contributed to the reduction of stem cell transcription factor SOX2 expression in CRC cells. Consistently, overexpression of ANGPTL1 reduced liver metastasis, tumor growth, and tumorigenicity in tumor-bearing mice. ANGPTL1 expression was negatively correlated with CSC markers expression and poor clinical outcomes in CRC patients. Taken together, these findings demonstrate that the molecular mechanisms of ANGPTL1 in colorectal cancer stem cell progression may provide a novel therapeutic strategy for CRC. (© 2022 The Author(s).)
Databáze:	MEDLINE
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