N-glycosylation of ACTRIIB enhances protein stability leading to rapid cell proliferation and strong resistance to docetaxel in nasopharyngeal carcinoma
Nasopharyngeal carcinoma (NPC) is a malignant tumor predominantly influenced by Epstein-Barr virus infection and genetic factors. The transforming growth factor-beta (TGF-β) superfamily is implicated in various cellular processes, including tumorigenesis. This study aimed to detect the role of one T...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Associação Brasileira de Divulgação Científica
2025-02-01
|
| Series: | Brazilian Journal of Medical and Biological Research |
| Subjects: | |
| Online Access: | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2025000100612&lng=en&tlng=en |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850189690763739136 |
|---|---|
| author | Qin Qin Junfeng Li Yinjian Shao Lan Liu Zhibin Luo |
| author_facet | Qin Qin Junfeng Li Yinjian Shao Lan Liu Zhibin Luo |
| author_sort | Qin Qin |
| collection | DOAJ |
| description | Nasopharyngeal carcinoma (NPC) is a malignant tumor predominantly influenced by Epstein-Barr virus infection and genetic factors. The transforming growth factor-beta (TGF-β) superfamily is implicated in various cellular processes, including tumorigenesis. This study aimed to detect the role of one TGF-β superfamily member activin receptor type IIB (ACTRIIB) in NPC. This study analyzed NPC datasets, including GSE12452, GSE102349, and GSE53819. ACTRIIB expression and N-glycosylation levels were assessed by western blot, real-time PCR, immunofluorescence, and immunohistochemistry in NPC cells and tissues. As indicated by the datasets, ACTRIIB was significantly upregulated in NPC tissues, and the up-regulation was associated with poor prognosis. This study confirmed the N-glycosylation of ACTRIIB primarily at the forty-second amino acid, an asparagine. The N-glycosylation of ACTRIIB promoted the localization of ACTRIIB to the cell membrane and prevented the degradation of the protein by lysosomes, through which ACTRIIB activated the downstream Smard1/2 to promote tumor cell proliferation and invasion. Inhibition of N-glycosylation or knockdown of ACTRIIB resulted in reduced cell proliferation and invasion and increased the cell sensitivity to docetaxel. In conclusion, N-glycosylation of ACTRIIB was a critical post-translational modification that enhanced protein stability and induced membrane localization, which facilitates the functions of ACTRIIB in cell proliferation and invasion in NPC. Inhibition of ACTRIIB N-glycosylation could potentially serve as a therapeutic strategy to improve the efficacy of chemotherapy in NPC. |
| format | Article |
| id | doaj-art-d7354348fafb4c5aa766e4a6568afb84 |
| institution | OA Journals |
| issn | 1414-431X |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Associação Brasileira de Divulgação Científica |
| record_format | Article |
| series | Brazilian Journal of Medical and Biological Research |
| spelling | doaj-art-d7354348fafb4c5aa766e4a6568afb842025-08-20T02:15:33ZengAssociação Brasileira de Divulgação CientíficaBrazilian Journal of Medical and Biological Research1414-431X2025-02-015810.1590/1414-431x2024e14368N-glycosylation of ACTRIIB enhances protein stability leading to rapid cell proliferation and strong resistance to docetaxel in nasopharyngeal carcinomaQin Qinhttps://orcid.org/0009-0004-1433-3305Junfeng Lihttps://orcid.org/0009-0009-1233-8926Yinjian Shaohttps://orcid.org/0009-0002-5951-0526Lan Liuhttps://orcid.org/0009-0009-1916-8886Zhibin Luohttps://orcid.org/0009-0002-8338-4064Nasopharyngeal carcinoma (NPC) is a malignant tumor predominantly influenced by Epstein-Barr virus infection and genetic factors. The transforming growth factor-beta (TGF-β) superfamily is implicated in various cellular processes, including tumorigenesis. This study aimed to detect the role of one TGF-β superfamily member activin receptor type IIB (ACTRIIB) in NPC. This study analyzed NPC datasets, including GSE12452, GSE102349, and GSE53819. ACTRIIB expression and N-glycosylation levels were assessed by western blot, real-time PCR, immunofluorescence, and immunohistochemistry in NPC cells and tissues. As indicated by the datasets, ACTRIIB was significantly upregulated in NPC tissues, and the up-regulation was associated with poor prognosis. This study confirmed the N-glycosylation of ACTRIIB primarily at the forty-second amino acid, an asparagine. The N-glycosylation of ACTRIIB promoted the localization of ACTRIIB to the cell membrane and prevented the degradation of the protein by lysosomes, through which ACTRIIB activated the downstream Smard1/2 to promote tumor cell proliferation and invasion. Inhibition of N-glycosylation or knockdown of ACTRIIB resulted in reduced cell proliferation and invasion and increased the cell sensitivity to docetaxel. In conclusion, N-glycosylation of ACTRIIB was a critical post-translational modification that enhanced protein stability and induced membrane localization, which facilitates the functions of ACTRIIB in cell proliferation and invasion in NPC. Inhibition of ACTRIIB N-glycosylation could potentially serve as a therapeutic strategy to improve the efficacy of chemotherapy in NPC.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2025000100612&lng=en&tlng=enN-glycosylationACTRIIBNasopharyngeal carcinomaDocetaxelMembrane localization |
| spellingShingle | Qin Qin Junfeng Li Yinjian Shao Lan Liu Zhibin Luo N-glycosylation of ACTRIIB enhances protein stability leading to rapid cell proliferation and strong resistance to docetaxel in nasopharyngeal carcinoma Brazilian Journal of Medical and Biological Research N-glycosylation ACTRIIB Nasopharyngeal carcinoma Docetaxel Membrane localization |
| title | N-glycosylation of ACTRIIB enhances protein stability leading to rapid cell proliferation and strong resistance to docetaxel in nasopharyngeal carcinoma |
| title_full | N-glycosylation of ACTRIIB enhances protein stability leading to rapid cell proliferation and strong resistance to docetaxel in nasopharyngeal carcinoma |
| title_fullStr | N-glycosylation of ACTRIIB enhances protein stability leading to rapid cell proliferation and strong resistance to docetaxel in nasopharyngeal carcinoma |
| title_full_unstemmed | N-glycosylation of ACTRIIB enhances protein stability leading to rapid cell proliferation and strong resistance to docetaxel in nasopharyngeal carcinoma |
| title_short | N-glycosylation of ACTRIIB enhances protein stability leading to rapid cell proliferation and strong resistance to docetaxel in nasopharyngeal carcinoma |
| title_sort | n glycosylation of actriib enhances protein stability leading to rapid cell proliferation and strong resistance to docetaxel in nasopharyngeal carcinoma |
| topic | N-glycosylation ACTRIIB Nasopharyngeal carcinoma Docetaxel Membrane localization |
| url | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2025000100612&lng=en&tlng=en |
| work_keys_str_mv | AT qinqin nglycosylationofactriibenhancesproteinstabilityleadingtorapidcellproliferationandstrongresistancetodocetaxelinnasopharyngealcarcinoma AT junfengli nglycosylationofactriibenhancesproteinstabilityleadingtorapidcellproliferationandstrongresistancetodocetaxelinnasopharyngealcarcinoma AT yinjianshao nglycosylationofactriibenhancesproteinstabilityleadingtorapidcellproliferationandstrongresistancetodocetaxelinnasopharyngealcarcinoma AT lanliu nglycosylationofactriibenhancesproteinstabilityleadingtorapidcellproliferationandstrongresistancetodocetaxelinnasopharyngealcarcinoma AT zhibinluo nglycosylationofactriibenhancesproteinstabilityleadingtorapidcellproliferationandstrongresistancetodocetaxelinnasopharyngealcarcinoma |