Clinical Science | VOL. 136
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ANGPTL1 attenuates cancer migration, invasion, and stemness through regulating FOXO3a-mediated SOX2 expression in colorectal cancer

Publication Date May 1, 2022

Abstract

Abstract 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.

Concepts

Clinical Outcomes In Colorectal Cancer Patients Outcomes In Colorectal Cancer Patients Expression In Colorectal Cancer Cells Cancer Invasion Therapeutic Strategy For Colorectal Cancer Cancer Stem Cell Markers Expression Colorectal Cancer Stemness In Colorectal Cancer Poor Clinical Outcomes Cancer Stem Cell Markers

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No potential conflict of interest was reported by the authors. The conception and design of the study, acquisition of data, analysis and interpretatio...

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