:
Cullin 4A (Cul4A) is overexpressed in a number of
cancers and has been established as an oncogene. This study aimed to elucidate the role of Cul4A in
lung cancer invasion and
metastasis. We observed that Cul4A was overexpressed in
non-small cell lung cancer (NSCLC) tissues and the overexpression of Cul4A was associated with poor prognosis after surgical resection and it also decreased the expression of the
tumor suppressor protein annexin A10 (ANXA10). The knockdown of Cul4A was associated with the upregulation of ANXA10, and the forced expression of Cul4A was associated with the downregulation of ANXA10 in
lung cancer cells. Further studies showed that the knockdown of Cul4A inhibited the invasion and
metastasis of
lung cancer cells, which was reversed by the further knockdown of ANXA10. In addition, the knockdown of Cul4A inhibited lung
tumor metastasis in mouse tail vein injection xenograft models. Notably, Cul4A regulated the degradation of ANXA10 through its interaction with ANXA10 and ubiquitination in
lung cancer cells. Our findings suggest that Cul4A is a prognostic marker in NSCLC patients, and Cul4A plays important roles in
lung cancer invasion and
metastasis through the regulation of the ANXA10
tumor suppressor.