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- Zhou, XY, et al.
(författare)
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Mechanisms of Anergic Inflammatory Response in Nasopharyngeal Carcinoma Cells Despite Ubiquitous Constitutive NF-κB Activation
- 2022
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Ingår i: Frontiers in cell and developmental biology. - : Frontiers Media SA. - 2296-634X. ; 10, s. 861916-
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Tidskriftsartikel (refereegranskat)abstract
- Commensal microbes cross talk with their colonized mucosa. We show that microbes and their cell wall components induce an inflammatory response in cultured human mucosal cells derived from the nonmalignant nasopharyngeal epithelium (NNE) cells in vitro. NNE cells show significant induction of NF-κB with nuclear shuttling and inflammatory gene response when exposed to Gram-positive bacteria (streptococci) or peptidoglycan (PGN), a component of the Gram-positive bacterial cell wall. This response is abrogated in nasopharyngeal carcinoma (NPC)–derived cell lines. The inflammatory response induced by NF-κB signaling was blocked at two levels in the tumor-derived cells. We found that NF-κB was largely trapped in lipid droplets (LDs) in the cytoplasm of the NPC-derived cells, while the increased expression of lysine-specific histone demethylase 1 (LSD1, a repressive nuclear factor) reduces the response mediated by remaining NF-κB at the promoters responding to inflammatory stimuli. This refractory response in NPC cells might be a consequence of long-term exposure to microbes in vivo during carcinogenic progression. It may contribute to the decreased antitumor immune responses in NPC, among others despite heavy T-helper cell infiltration, and thus facilitate tumor progression.
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- Liang, JZ, et al.
(författare)
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Epstein-Barr virus-encoded LMP2A stimulates migration of nasopharyngeal carcinoma cells via the EGFR/Ca2+/calpain/ITGβ4 axis
- 2017
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Ingår i: Biology open. - : The Company of Biologists. - 2046-6390. ; 6:6, s. 914-922
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Tidskriftsartikel (refereegranskat)abstract
- Epstein-Barr virus (EBV)-encoded latent membrane protein 2A (LMP2A) promotes the motility of nasopharyngeal carcinoma (NPC) cells. Previously, we have shown that the localization of integrin β4 (ITGβ4) was regulated by LMP2A, with ITGβ4 concentrated at the cellular protrusions in LMP2A expressing NPC cells. In the present study, we aim to further investigate mechanisms involved in this process and its contribution to cell motility. We show that expression of LMP2A was correlated with increased EGFR activation, elevated levels of intracellular Ca2+, calpain activation and accelerated cleavage of ITGβ4. Activation of EGFR and calpain activity was responsible for a redistribution of ITGβ4 from the basal layer of NPC cells, to peripheral membrane structures, which correlated with an increased migratory capacity of NPC cells. Furthermore, we demonstrated that the calpain inhibitor calpastatin was downregulated in NPC primary tumors. In conclusion, our results point to LMP2A-mediated targeting of the EGFR/Ca2+/calpain/ITGβ4 signaling system as a mechanism underlying the increased motility of NPC cells. We suggest that calpain-facilitated cleavage of ITGβ4 contributes to the malignant phenotype of NPC cells.
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