| Autor: |
Chunlin Lin, Penghang Lin, Huayan Lin, Hengxin Yao, Songyi Liu, Ruofan He, Hui Chen, Zuhong Teng, Robert M. Hoffman, Jianxin Ye, Guangwei Zhu |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
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| Zdroj: |
Oncogenesis, Vol 12, Iss 1, Pp 1-16 (2023) |
| Druh dokumentu: |
article |
| ISSN: |
2157-9024 |
| DOI: |
10.1038/s41389-023-00488-w |
| Popis: |
Abstract Colorectal cancer (CRC) is a formidable disease due to the intricate mechanisms that drive its proliferation and metastasis. Despite significant progress in cancer research, the integration of these mechanisms that influence cancer cell behavior remains elusive. Therefore, it is imperative to comprehensively elucidate the underlying mechanisms driving CRC proliferation and metastasis. In this study, we reported a novel role of SLC26A3 in suppressing CRC progression. We found that SLC26A3 expression was downregulated in CRC, which was proportionally correlated with survival. Our in vivo and in vitro experiments demonstrated that up-regulation of SLC26A3 inhibited CRC proliferation and metastasis, while down-regulation of SLC26A3 promoted CRC progression by modulating the expression level of IκB. Furthermore, we identified NHERF2 as a novel interacting protein of SLC26A3 responsible for stabilizing the IκB protein and removing ubiquitination modification. Mechanistically, SLC26A3 augmented the interaction between NHERF2 and IκB, subsequently reducing its degradation. This process inhibited the dissociation of p65 from the IκB/p65/p50 complex and reduced the translocation of p65 from the cytoplasm to the nucleus. Moreover, our investigation revealed that NF-κB/p65 directly bound to the promoter of SLC26A3, leading to a decline in its mRNA expression. Thus, SLC26A3 impeded the nuclear translocation of NF-κB/p65, enhancing the transcription of SLC26A3 and establishing a positive regulatory feedback loop in CRC cells. Collectively, these results suggest that a SLC26A3/NHERF2-IκB/NF-κB/p65 signaling loop suppresses proliferation and metastasis in CRC cells. These findings propose a novel SLC26A3-driven signaling loop that regulates proliferation and metastasis in CRC, providing promising therapeutic interventions and prognostic targets for the management of CRC. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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