CCL18 promotes the invasion and metastasis of breast cancer through Annexin A2.
Oncol Rep
; 43(2): 571-580, 2020 02.
Article
en En
| MEDLINE
| ID: mdl-31894281
ABSTRACT
Chemokine (CC motif) ligand 18 (CCL18) is derived from breast tumorassociated macrophages (TAMs), which are primarily a macrophage subpopulation with an M2 phenotype. CCL18 binds to its receptor, PYK2 Nterminal domain interacting receptor 1 (Nir1), and promotes tumor progression and metastasis by inducing epithelialmesenchymal transition (EMT) via the PI3K/Akt/GSK3ß/Snail signaling pathway in breast cancer cells. Recent research shows that Annexin A2 (AnxA2) plays a significant role in the invasion, metastasis, angiogenesis, proliferation, Factin polymerization and multidrug resistance to chemotherapy of breast cancer. The present study aimed to elucidate the molecular mechanisms by which CCL18 promotes breast cancer progression through AnxA2 which are not fully understood. Western blot analysis showed that the expression of AnxA2 was upregulated in highly invasive breast cancer cell lines and invasive ductal carcinoma. Furthermore, through chemotaxis, scratch, Matrigel invasion, and spontaneous metastasis assays, it was demonstrated that AnxA2 enhanced the invasion of breast cancer cells and the metastasis of human breast cancer cells to lungs of SCID mice with CCL18 stimulation. Cellular Factin measurement assay showed that reduction of AnxA2 suppressed CCL18induced Factin polymerization though phosphorylation of integrin ß1 in breast cancer cells. Immunofluorescence and western blot analysis revealed that AnxA2 promoted CCL18induced EMT via the PI3K/Akt/GSK3ß/Snail signaling pathway, and LY294002 inhibited the phosphorylation of AnxA2 in vitro. In brief, AnxA2, as a downstream molecule of Nir 1 binding to CCL18, promotes invasion and metastasis by EMT through the PI3K/Akt/GSK3ß/Snail signaling pathway in breast cancer. This study suggests that AnxA2 is a potential antiinvasion/metastasis target for therapeutic intervention in breast cancer.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias de la Mama
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Anexina A2
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Carcinoma Ductal de Mama
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Quimiocinas CC
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Neoplasias Pulmonares
Límite:
Adult
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Aged
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Animals
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Female
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Humans
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Middle aged
Idioma:
En
Año:
2020
Tipo del documento:
Article