Quantitative glycoproteomics analysis identifies novel FUT8 targets and signaling networks critical for breast cancer cell invasiveness
Abstract Background We recently showed that fucosyltransferase 8 (FUT8)-mediated core fucosylation of transforming growth factor-β receptor enhances its signaling and promotes breast cancer invasion and metastasis. However, the complete FUT8 target glycoproteins and their downstream signaling networ...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2022-03-01
|
| Series: | Breast Cancer Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13058-022-01513-3 |
| _version_ | 1818321132602785792 |
|---|---|
| author | Cheng-Fen Tu Fu-An Li Ling-Hui Li Ruey-Bing Yang |
| author_facet | Cheng-Fen Tu Fu-An Li Ling-Hui Li Ruey-Bing Yang |
| author_sort | Cheng-Fen Tu |
| collection | DOAJ |
| description | Abstract Background We recently showed that fucosyltransferase 8 (FUT8)-mediated core fucosylation of transforming growth factor-β receptor enhances its signaling and promotes breast cancer invasion and metastasis. However, the complete FUT8 target glycoproteins and their downstream signaling networks critical for breast cancer progression remain largely unknown. Method We performed quantitative glycoproteomics with two highly invasive breast cancer cell lines to unravel a comprehensive list of core-fucosylated glycoproteins by comparison to parental wild-type and FUT8-knockout counterpart cells. In addition, ingenuity pathway analysis (IPA) was performed to highlight the most enriched biological functions and signaling pathways mediated by FUT8 targets. Novel FUT8 target glycoproteins with biological interest were functionally studied and validated by using LCA (Lens culinaris agglutinin) blotting and LC–MS/MS (liquid chromatography–tandem mass spectrometry) analysis. Results Loss-of-function studies demonstrated that FUT8 knockout suppressed the invasiveness of highly aggressive breast carcinoma cells. Quantitative glycoproteomics identified 140 common target glycoproteins. Ingenuity pathway analysis (IPA) of these target proteins gave a global and novel perspective on signaling networks essential for breast cancer cell migration and invasion. In addition, we showed that core fucosylation of integrin αvβ5 or IL6ST might be crucial for breast cancer cell adhesion to vitronectin or enhanced cellular signaling to interleukin 6 and oncostatin M, two cytokines implicated in the breast cancer epithelial–mesenchymal transition and metastasis. Conclusions Our report reveals a comprehensive list of core-fucosylated target proteins and provides novel insights into signaling networks crucial for breast cancer progression. These findings will assist in deciphering the complex molecular mechanisms and developing diagnostic or therapeutic approaches targeting these signaling pathways in breast cancer metastasis. |
| first_indexed | 2024-12-13T10:36:03Z |
| format | Article |
| id | doaj.art-60314cc7a70a412882c45c08bb050d3e |
| institution | Directory Open Access Journal |
| issn | 1465-542X |
| language | English |
| last_indexed | 2024-12-13T10:36:03Z |
| publishDate | 2022-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Breast Cancer Research |
| spelling | doaj.art-60314cc7a70a412882c45c08bb050d3e2022-12-21T23:50:44ZengBMCBreast Cancer Research1465-542X2022-03-0124111810.1186/s13058-022-01513-3Quantitative glycoproteomics analysis identifies novel FUT8 targets and signaling networks critical for breast cancer cell invasivenessCheng-Fen Tu0Fu-An Li1Ling-Hui Li2Ruey-Bing Yang3Institute of Biomedical Sciences, Academia SinicaInstitute of Biomedical Sciences, Academia SinicaInstitute of Biomedical Sciences, Academia SinicaInstitute of Biomedical Sciences, Academia SinicaAbstract Background We recently showed that fucosyltransferase 8 (FUT8)-mediated core fucosylation of transforming growth factor-β receptor enhances its signaling and promotes breast cancer invasion and metastasis. However, the complete FUT8 target glycoproteins and their downstream signaling networks critical for breast cancer progression remain largely unknown. Method We performed quantitative glycoproteomics with two highly invasive breast cancer cell lines to unravel a comprehensive list of core-fucosylated glycoproteins by comparison to parental wild-type and FUT8-knockout counterpart cells. In addition, ingenuity pathway analysis (IPA) was performed to highlight the most enriched biological functions and signaling pathways mediated by FUT8 targets. Novel FUT8 target glycoproteins with biological interest were functionally studied and validated by using LCA (Lens culinaris agglutinin) blotting and LC–MS/MS (liquid chromatography–tandem mass spectrometry) analysis. Results Loss-of-function studies demonstrated that FUT8 knockout suppressed the invasiveness of highly aggressive breast carcinoma cells. Quantitative glycoproteomics identified 140 common target glycoproteins. Ingenuity pathway analysis (IPA) of these target proteins gave a global and novel perspective on signaling networks essential for breast cancer cell migration and invasion. In addition, we showed that core fucosylation of integrin αvβ5 or IL6ST might be crucial for breast cancer cell adhesion to vitronectin or enhanced cellular signaling to interleukin 6 and oncostatin M, two cytokines implicated in the breast cancer epithelial–mesenchymal transition and metastasis. Conclusions Our report reveals a comprehensive list of core-fucosylated target proteins and provides novel insights into signaling networks crucial for breast cancer progression. These findings will assist in deciphering the complex molecular mechanisms and developing diagnostic or therapeutic approaches targeting these signaling pathways in breast cancer metastasis.https://doi.org/10.1186/s13058-022-01513-3Breast cancerCore fucosylationFUT8GlycoproteomicsMetastasis |
| spellingShingle | Cheng-Fen Tu Fu-An Li Ling-Hui Li Ruey-Bing Yang Quantitative glycoproteomics analysis identifies novel FUT8 targets and signaling networks critical for breast cancer cell invasiveness Breast Cancer Research Breast cancer Core fucosylation FUT8 Glycoproteomics Metastasis |
| title | Quantitative glycoproteomics analysis identifies novel FUT8 targets and signaling networks critical for breast cancer cell invasiveness |
| title_full | Quantitative glycoproteomics analysis identifies novel FUT8 targets and signaling networks critical for breast cancer cell invasiveness |
| title_fullStr | Quantitative glycoproteomics analysis identifies novel FUT8 targets and signaling networks critical for breast cancer cell invasiveness |
| title_full_unstemmed | Quantitative glycoproteomics analysis identifies novel FUT8 targets and signaling networks critical for breast cancer cell invasiveness |
| title_short | Quantitative glycoproteomics analysis identifies novel FUT8 targets and signaling networks critical for breast cancer cell invasiveness |
| title_sort | quantitative glycoproteomics analysis identifies novel fut8 targets and signaling networks critical for breast cancer cell invasiveness |
| topic | Breast cancer Core fucosylation FUT8 Glycoproteomics Metastasis |
| url | https://doi.org/10.1186/s13058-022-01513-3 |
| work_keys_str_mv | AT chengfentu quantitativeglycoproteomicsanalysisidentifiesnovelfut8targetsandsignalingnetworkscriticalforbreastcancercellinvasiveness AT fuanli quantitativeglycoproteomicsanalysisidentifiesnovelfut8targetsandsignalingnetworkscriticalforbreastcancercellinvasiveness AT linghuili quantitativeglycoproteomicsanalysisidentifiesnovelfut8targetsandsignalingnetworkscriticalforbreastcancercellinvasiveness AT rueybingyang quantitativeglycoproteomicsanalysisidentifiesnovelfut8targetsandsignalingnetworkscriticalforbreastcancercellinvasiveness |