SPON2 Promotes M1-like Macrophage Recruitment and Inhibits Hepatocellular Carcinoma Metastasis by Distinct Integrin-Rho GTPase-Hippo Pathways
- Title
- SPON2 Promotes M1-like Macrophage Recruitment and Inhibits Hepatocellular Carcinoma Metastasis by Distinct Integrin-Rho GTPase-Hippo Pathways
- Author
- 이수재
- Keywords
- MATRIX PROTEIN MINDIN; PATTERN-RECOGNITION MOLECULE; TUMOR-ASSOCIATED MACROPHAGES; EXTRACELLULAR-MATRIX; CELL-MIGRATION; STRESS FIBERS; CANCER; SPONDIN-2; LIVER; MICROENVIRONMENTS
- Issue Date
- 2018-05
- Publisher
- AMER ASSOC CANCER RESEARCH
- Citation
- CANCER RESEARCH, v. 78, no. 9, page. 2305-2317
- Abstract
- Tumor-associated macrophages (TAM) represent key regulators of the complex interplay between cancer and the immune microenvironment. Matricellular protein SPON2 is essential for recruiting lymphocytes and initiating immune responses. Recent studies have shown that SPON2 has complicated roles in cell migration and tumor progression. Here we report that, in the tumor microenvironment of hepatocellular carcinoma (HCC), SPON2 not only promotes infiltration of M1-like macrophages but also inhibits tumor metastasis. SPON2-alpha 4 beta 1 integrin signaling activated RhoA and Rac1, increased F-actin reorganization, and promoted M1-like macrophage recruitment. F-Actin accumulation also activated the Hippo pathway by suppressing LATS1 phosphorylation, promoting YAP nuclear translocation, and initiating downstream gene expression. However, SPON2-alpha 5 beta 1 integrin signaling inactivated RhoA and prevented F-actin assembly, thereby inhibiting HCC cell migration; the Hippo pathway was not noticeably involved in SPON2-mediated HCC cell migration. In HCC patients, SPON2 levels correlated positively with prognosis. Overall, our findings provide evidence that SPON2 is a critical factor in mediating the immune response against tumor cell growth and migration in HCC.Significance: Matricellular protein SPON2 acts as an HCC suppressor and utilizes distinct signaling events to perform dual functions in HCC microenvironment. (C) 2018 AACR.
- URI
- https://cancerres.aacrjournals.org/content/78/9/2305https://repository.hanyang.ac.kr/handle/20.500.11754/118796
- ISSN
- 0008-5472; 1538-7445
- DOI
- 10.1158/0008-5472.CAN-17-2867
- Appears in Collections:
- COLLEGE OF NATURAL SCIENCES[S](자연과학대학) > LIFE SCIENCE(생명과학과) > Articles
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