Target intelligence / Profile preview

Sperm-associated antigen 5 (SPAG5)

Target
SPAG5
Molecular classification
Other (Mitotic spindle-associated protein), Cell cycle protein
01

Overview

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].

Other names
AstrinMAP126Mitotic spindle-associated protein p126Mitotic spindle coiled-coil related proteinhMAP126Deepest
02

Mechanism of action

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].

03

Biological functions

Chromosome segregationProgression into anaphaseRegulation of spindle assemblyKinetochore-microtubule attachmentCell cycle progressionMaintenance of centrosome integrityCentriole duplicationSuppression of mTORC1 activity under stressCell proliferationApoptosis resistance (via mTORC1 pathway, stress granule recruitment)
04

Disease associations

Cancer (notably breast, hepatocellular, lung, gastric, and endometrial carcinoma)Cancer testis antigen (CTA, found in tumors with limited normal tissue expression)Prognostic marker for poor survival in cancerChemotherapy sensitivity predictorMicrocephaly (rare, germline mutation context)
05

Safety considerations

Not specifically reported; as a core mitotic spindle regulator, systemic inhibition could risk myelosuppression or toxicity in dividing normal cells (general for mitotic spindle inhibitors).No marketed drugs specifically target SPAG5 directly; current targeting is experimental (e.g., curcumin in lab settings)[1].
06

Interacting drugs

Curcumin
07

Biomarkers

High SPAG5 expression serves as a proliferation marker and is associated with poor prognosis in several cancers[2][3].Used to predict chemotherapy sensitivity, especially in breast cancer[2].Possible immune response/immunotherapy response marker (related to immune checkpoint expression and immune cell infiltration in endometrial carcinoma)[3].

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