PLXNC1
Overview
PLXNC1 (Plexin C1, also known as VESPR) is a canonical receptor for class 7 semaphorins (SEMA7A). While PLXNC1 was historically considered the primary receptor mediating SEMA7A signaling, functional studies in gallbladder cancer have demonstrated that PLXNC1 is dispensable for SEMA7A-induced epithelial-mesenchymal transition (EMT) and cancer stemness, with ITGB1 (integrin beta-1) serving as the functionally relevant receptor in this context.
Alterations observed in the corpus
- PLXNC1 is the canonical SEMA7A receptor but is not required for SEMA7A-induced GBC EMT or stemness: PLXNC1 shRNA blocked PAK phosphorylation but did not inhibit invasion, EMT marker changes, or tumorsphere formation in GBC-SD/NOZ cell lines; anti-PLXNC1 antibody had no effect on these phenotypes PMID:24997986
Cancer types (linked)
- GBC: PLXNC1 expressed in GBC cells but functionally dispensable for SEMA7A-driven tumor-promoting signaling; ITGB1 is the operative receptor for SEMA7A-mediated invasion and stemness PMID:24997986
Co-occurrence and mutual exclusivity
- Co-expressed with SEMA7A in GBC context; however, ITGB1 (not PLXNC1) mediates the functionally relevant SEMA7A/AKT/p300 axis PMID:24997986
Therapeutic relevance
- Targeting PLXNC1 is unlikely to disrupt SEMA7A-driven pro-tumorigenic signaling in GBC based on functional data; ITGB1 blockade or downstream PI3K/p300 inhibition are the supported intervention points PMID:24997986
Open questions
- Whether PLXNC1 mediates immune-modulatory SEMA7A functions (distinct from tumor-cell-intrinsic EMT/stemness) in the GBC tumor microenvironment is not addressed.
- The relative roles of PLXNC1 vs ITGB1 in other cancer types where SEMA7A is active remain uncharacterized.
Sources
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