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Sperm-associated antigen 5 (SPAG5), also known as Astrin or MAP126, is a conserved spindle-associated protein essential for mitosis. It regulates mitotic spindle formation, chromosome alignment, kinetochore-microtubule attachment, and the timing of chromatid segregation and anaphase progression[4][5][6]. SPAG5 is active during cell division, localizing to the spindle and centrosome and promoting centrosome integrity, centriole duplication, and orderly mitotic progression. Aberrant upregulation or mutation of SPAG5 is linked to increased cell proliferation, oncogenesis, and poor clinical outcome in multiple tumor types, including breast, liver, lung, stomach, and endometrial cancer[1][2][3][6]. As a cancer/testis antigen, it is generally absent from normal adult tissues except testis and placenta. High SPAG5 expression in tumors correlates with poor prognosis and chemoresistance and may affect immune cell infiltration and immunotherapy responses in some cancers[3]. Experimentally, SPAG5 is inhibited by curcumin, leading to increased apoptosis of cancer cells, highlighting its potential as a novel anti-mitotic therapeutic target[1].
Targeting SPAG5 can impair mitotic progression, increase apoptosis, and reduce proliferation and migration in cancer cells (notably by interfering with spindle assembly and disrupting the Wnt/β-catenin and Hippo signaling pathways)[1][2][3][6].
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