Abstract: Cullin 4A (Cul4A) is overexpressed in a number of cancers and has been established as an\noncogene. This study aimed to elucidate the role of Cul4A in lung cancer invasion and metastasis.\nWe observed that Cul4A was over expressed in non-small cell lung cancer (NSCLC) tissues and the\nover expression of Cul4A was associated with poor prognosis after surgical resection and it also\ndecreased the expression of the tumor suppressor protein annexin A10 (ANXA10). The knockdown\nof Cul4A was associated with the upregulation of ANXA10, and the forced expression of Cul4A was\nassociated with the down regulation of ANXA10 in lung cancer cells. Further studies showed that\nthe knockdown of Cul4A inhibited the invasion and metastasis of lung cancer cells, which was\nreversed by the further knockdown of ANXA10. In addition, the knockdown of Cul4A inhibited\nlung tumor metastasis in mouse tail vein injection xenograft models. Notably, Cul4A regulated the\ndegradation of ANXA10 through its interaction with ANXA10 and ubiquitination in lung cancer\ncells. Our findings suggest that Cul4A is a prognostic marker in NSCLC patients, and Cul4A plays\nimportant roles in lung cancer invasion and metastasis through the regulation of the ANXA10 tumor\nsuppressor.
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