Model for regulation of MSMP expression in cancer cells and its proangiogenic role in ovarian tumors (Homo sapiens)

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1Tumor cellNucleusEndothelial cellHypoxiaEnhancerMAPK SignalingCCR2AngiogenesisMSMPCTCFCCR2MSMP


Proposed model for regulation of MSMP expression in cancer cells under hypoxic conditions and the proangiogenic role of MSMP in ovarian tumors.

The recruitment of the transcriptional repressor CTCF to the MSMP enhancer region is regulated by changes in H3 acetylation of the MSMP enhancer. In hypoxic conditions, the repressor-enhancer binding is disrupted, leading to increased expression of MSMP. Secretion of MSMP triggers MAPK signaling in endothelial cells (presumably via CCR2 signaling), which promotes angiogenesis.

This suggests that MSMP inhibition in combination with antiangiogenesis drugs (anti-VEGF) could be a new strategy to overcome resistance to antiangiogenesis therapy.

Description adapted from Mitamura et al.

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  1. Mitamura T, Pradeep S, McGuire M, Wu SY, Ma S, Hatakeyama H, Lyons YA, Hisamatsu T, Noh K, Villar-Prados A, Chen X, Ivan C, Rodriguez-Aguayo C, Hu W, Lopez-Berestein G, Coleman RL, Sood AK; ''Induction of anti-VEGF therapy resistance by upregulated expression of microseminoprotein (MSMP).''; Oncogene, 2018 PubMed Europe PMC


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98987view20:37, 19 October 2018KhanspersModified description
98986view20:37, 19 October 2018KhanspersModified description
98985view20:27, 19 October 2018KhanspersOntology Term : 'endothelial cell' added !
98984view20:27, 19 October 2018KhanspersOntology Term : 'CC chemokine mediated signaling pathway' added !
98983view20:25, 19 October 2018KhanspersOntology Term : 'ovarian cancer' added !
98982view20:24, 19 October 2018KhanspersNew pathway

External references


NameTypeDatabase referenceComment
AngiogenesisPathwayWP1539 (WikiPathways)
CCR2GeneProductENSG00000121807 (Ensembl)
CTCFGeneProductENSG00000102974 (Ensembl)
MAPK SignalingPathwayWP382 (WikiPathways)
MSMPGeneProductENSG00000215183 (Ensembl)

Annotated Interactions

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