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Suppression of migration, invasion, and metastasis of cisplatin-resistant head and neck squamous cell carcinoma through IKK? inhibition.


ABSTRACT: We explored the role of the transcription factor, NF-?B, and its upstream kinase IKK? in regulation of migration, invasion, and metastasis of cisplatin-resistant head and neck squamous cell carcinoma (HNSCC). We showed that cisplatin-resistant HNSCC cells have a stronger ability to migrate and invade, as well as display higher IKK?/NF-?B activity compared to their parental partners. Importantly, we found that knockdown of IKK?, but not NF-?B, dramatically impaired cell migration and invasion in these cells. Consistent with this, the IKK? inhibitor, CmpdA, also inhibited cell migration and invasion. Previous studies have already shown that N-Cadherin, an epithelial-mesenchymal transition (EMT) marker, and IL-6, a pro-inflammatory cytokine, play important roles in regulation of HNSCC migration, invasion, and metastasis. We found that cisplatin-resistant HNSCC expressed higher levels of N-Cadherin and IL-6, which were significantly inhibited by CmpdA. More importantly, we showed that CmpdA treatment dramatically abated cisplatin-resistant HNSCC cell metastasis to lungs in a mouse model. Our data demonstrated the crucial role of IKK? in control of migration, invasion, and metastasis, and implicated that targeting IKK? may be a potential therapy for cisplatin-resistant metastatic HNSCC.

SUBMITTER: Liao J 

PROVIDER: S-EPMC7305835 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Suppression of migration, invasion, and metastasis of cisplatin-resistant head and neck squamous cell carcinoma through IKKβ inhibition.

Liao Jipei J   Yang Zejia Z   Carter-Cooper Brandon B   Chang Elizabeth T ET   Choi Eun Yong EY   Kallakury Bhaskar B   Liu Xuefeng X   Lapidus Rena G RG   Cullen Kevin J KJ   Dan Hancai H  

Clinical & experimental metastasis 20200204 2


We explored the role of the transcription factor, NF-κB, and its upstream kinase IKKβ in regulation of migration, invasion, and metastasis of cisplatin-resistant head and neck squamous cell carcinoma (HNSCC). We showed that cisplatin-resistant HNSCC cells have a stronger ability to migrate and invade, as well as display higher IKKβ/NF-κB activity compared to their parental partners. Importantly, we found that knockdown of IKKβ, but not NF-κB, dramatically impaired cell migration and invasion in  ...[more]

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