Differential Expression Patterns of Eph Receptors and Ephrin Ligands in Human Cancers

Table 6

Altered expression of Eph receptors and ephrin ligands in colorectal carcinoma.

Eph receptor/ephrin ligand	Preferred molecular interaction	↑/↓ relative to normal tissue	Mechanism	Reference
EphA1		↓/↑	(i) Heterogeneous expression with both elevated/depressed expression depending on stage of CRC; (ii) Low EphA1 expression strongly correlates with poor survival (); (1) EphA1 overexpression more prevalent in stage II CRC compared to stage III CRC (); (iii) EphA1 knockdown promotes spreading and adhesion of HRT18 cells; (1) Activation of ERK and c-Jun NH2-terminal kinase (JNK) signaling pathway with EphA1 knockdown; (iv) EphA1 down regulation via epigenetic silencing; (1) CpG islands in promoter region of EphA1 gene; (2) EphA1 reexpression after demethylating agent treatment	[97–100]
EphA2		↓/↑	(i) Heterogeneous expression with both elevated/depressed expression depending on stage of CRC; (1) Up to 5-fold increase of expression in CRC versus normal tissue; (ii) Higher EphA2 expression correlate with poor survival in stage II/III colorectal cancer tissues; (1) Downregulation of EphA2 via RNAi or recombinant EFNA1 suppressed migration and invasion in KRASMT CRC cells; (iii) EphA2 regulated by KRAS-driven MAPK and RalGGS-RalA pathway	[97, 101]
EphA3		↓	(i) Decreased in CRC tumor specimens; (ii) Overexpress, decreased expression and ectopic Eph3 expression had no effect on tumorigenesis in xenografts or mouse models	[97]
EphA7		↓	(i) EphA7 down regulation via epigenetic silencing; (1) CpG islands in promoter region of EphA7 gene	[97, 102, 103]
EphB2		↓	(i) Reduced in CRC compared to normal colorectal tissue; (1) Higher EphB2 correlates with better prognosis; (ii) Expression regulated by transcription p300 via TCF/B-catenin pathway	[104, 105]
EphB3	Ephrin-B1	↓	(i) Reduced EphB3 in advanced Duke’s stage tumor specimen; (ii) EphB4 overexpression resulted in inhibition of HT29 growth and inhibit epithelial to mesenchymal transition; (1) Activation of zonlua occludens-1, E-cadherin, and plakoglobin	[106, 107]
EphB4		↑	(i) Stable EphB4 overexpression in SW480 resulted in increased growth and invasion; (ii) Expression regulated by transcription CBP complex via TCF/B-catenin pathway	[97, 104, 105, 108, 109]
EphB6		↓	(i) Lower EphB6 correlates with poor cell differentiation, advance disease, metastatic spread, and poor prognosis; (ii) Xenograft and mouse models demonstrate sole loss of EphB6 to be insufficient to trigger tumorigenesis	[110, 111]