V-set and transmembrane domain-containing protein 2A (VSTM2A)

V-set and transmembrane domain-containing protein 2A (VSTM2A) is a secreted member of the immunoglobulin superfamily characterized by a single immunoglobulin V-set domain[1][3]. VSTM2A is expressed in specific tissues including normal brain, colorectal tissue, and kidney, but is downregulated in several cancers (notably, colorectal cancer and MTSCC)[2][3]. It functions predominantly as a tumor suppressor, acting through direct interaction with the Wnt signaling co-receptor LRP6 to inhibit Wnt/β-catenin pathway activation. This antagonism leads to suppression of cancer cell proliferation, survival, migration, and induces apoptosis. Additionally, VSTM2A has been implicated in the regulation of adipogenesis and possibly in modulation of immune responses due to structural similarity with proteins such as PD-1[1]. VSTM2A overexpression is a sensitive and specific diagnostic biomarker for MTSCC, and its loss is associated with poor colorectal cancer prognosis[2][3][4]. There are currently no direct drugs targeting VSTM2A, and therapeutic or toxicity data are unavailable.

Other names

VSTM2MGC33530hypothetical protein MGC33530V-set and transmembrane domain containing 2

Antagonism of Wnt signaling via direct binding to co-receptor LRP6, leading to inhibition of LRP6 phosphorylation and induction of receptor endocytosis and lysosomal degradation Possible antagonist of PD-L1 interaction with PD-1, suggesting an immunoregulatory mechanism[1]