127) Our finding suggests the novel type of regulation system of EGF signaling involving lectin-to-carbohydrate interaction and downregulation of ligand binding. |
PMID:24608429 DOI:10.1038/onc.2014.20 |
2015 Oncogene |
* Surfactant protein D suppresses lung cancer progression by downregulation of epidermal growth factor signaling. |
- Surfactant protein D (SP-D) is a member of the collectin family that has an important role in maintaining pulmonary homeostasis. In this study, we demonstrated that SP-D inhibited the proliferation, migration and invasion of A549 human lung adenocarcinoma cells. We found that SP-D suppressed epidermal growth factor (EGF) signaling in A549 cells, H441 human lung adenocarcinoma cells and human EGF receptor (EGFR) stable expression CHO-K1 cells. A binding study using (125)I-EGF demonstrated that SP-D downregulated the binding of EGF to EGFR. A ligand blot indicated that SP-D bound to EGFR, and a lectin blot suggested that EGFR in A549 cells had both high-mannose type and complex type N-glycans. We purified the recombinant extracellular domain of EGFR (soluble EGFR=soluble EGFR (sEGFR)), and demonstrated that SP-D directly bound to sEGFR in a Ca(2+)-dependent manner. The binding of SP-D to sEGFR was suppressed by EDTA, mannose or N-glycopeptidase F treatment. Mass spectrometric analysis indicated that N-glycans in domain III of EGFR were of a high-mannose type. These data suggest that SP-D reduces EGF binding to EGFR through the interaction between the carbohydrate recognition domain of SP-D and N-glycans of EGFR, and downregulates EGF signaling. Our finding suggests the novel type of regulation system of EGF signaling involving lectin-to-carbohydrate interaction and downregulation of ligand binding. |
(1)22 therapeutic | (17)3 mutation | (33)2 approaches | (49)2 information |
(2)11 and | (18)3 paradigm | (34)2 autosomal | (50)2 inhibitors |
(3)8 mechanism | (19)3 role | (35)2 candidate | (51)2 learning |
(4)8 method | (20)3 strain | (36)2 cardiac | (52)2 modulators |
(5)7 approach | (21)3 target | (37)2 clinical | (53)2 object |
(6)7 mutations | (22)3 targeted | (38)2 compounds | (54)2 oral |
(7)6 therapies | (23)3 targets | (39)2 data | (55)2 polymer |
(8)5 technique | (24)3 treatment | (40)2 described | (56)2 potent |
(9)4 strategies | (25)3 type | (41)2 dual | (57)2 prognostic |
(10)4 strategy | (26)3 words | (42)2 electroporation | (58)2 putative |
(11)4 surgical | (27)2 *null* | (43)2 finding | (59)2 recombinants |
(12)3 antibacterial | (28)2 anti-tumor | (44)2 findings | (60)2 results |
(13)3 drug | (29)2 antibiotic | (45)2 form | (61)2 therapeutical |
(14)3 homozygous | (30)2 anticancer | (46)2 genetic | (62)2 titanium |
(15)3 insights | (31)2 application | (47)2 imaging | (63)2 treatments |
(16)3 mechanisms | (32)2 applications | (48)2 in |
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