Collagen I-induced VCAN/ERK signaling and PARP1/ZEB1-mediated metastasis facilitate OSBPL2 defect to promote colorectal cancer progression

• DOI: 10.1038/s41419-024-06468-1
• Publication Date: 2024-01-24T14:14:53Z
• Authors: Kang Lin; Yun Zhao; Yuqi Tang; Ying Chen; Moubin Lin; Luwei He
• Keywords: Matricellular protein; Tumor progression

Abstract The global burden of colorectal cancer (CRC) has rapidly increased in recent years. Dysregulated cholesterol homeostasis facilitated by extracellular matrix (ECM) remodeling transforms the tumor microenvironment. Collagen I, a major with ECM component is highly expressed tumors infiltrative growth. Although oxysterol binding protein (OSBP)-related proteins accommodate tumorigenesis, OSBPL2, which usually involved deafness, not associated CRC progression. Therefore, we aimed to investigate pathological function OSBPL2 and identify molecular link between ECM-Collagen I facilitate development new treatments for CRC. predicted favorable prognosis stage IV substantially repressed I-induced focal adhesion, migration, invasion. reduction activated ERK signaling through VCAN/AREG/EREG axis during growth, while relying on PARP1 via ZEB1 metastasis. defect supported growth metastasis, were suppressed inhibitors SCH772984 AG14361, respectively. Overall, our findings revealed that loss aggravates progression VCAN-mediated PARP1/ZEB1 axis. This demonstrates AG14361 are reciprocally connective therapies Low CRC, could contribute further targeted treatment.