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Plexin-B3 expression stimulates MET signaling, breast cancer stem cell specification, and lung metastasis
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DOI：10.1016/j.celrep.2023.112164.png)
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Abstract
En 中文
Intratumoral hypoxia is a microenvironmental feature that promotes breast cancer progression and is asso-ciated with cancer mortality. Plexin B3 (PLXNB3) is highly expressed in estrogen receptor-negative breast cancer, but the underlying mechanisms and consequences have not been thoroughly investigated. Here, we report that PLXNB3 expression is increased in response to hypoxia and that PLXNB3 is a direct target gene of hypoxia-inducible factor 1 (HIF-1) in human breast cancer cells. PLXNB3 expression is correlated with HIF-1a immunohistochemistry, breast cancer grade and stage, and patient mortality. Mechanistically, PLXNB3 is required for hypoxia-induced MET/SRC/focal adhesion kinase (FAK) and MET/SRC/STAT3/ NANOG signaling as well as hypoxia-induced breast cancer cell migration, invasion, and cancer stem cell specification. PLXNB3 knockdown impairs tumor formation and lung metastasis in orthotopic breast cancer mouse models.
Keywords:
SEMAPHORIN 5A
AXON GUIDANCE
HYPOXIA
RECEPTOR
PROGNOSIS
CARCINOMA
INVASION
ALDH1
Journal
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6.9
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1.7W
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10.2W