Functional regulation of oestrogen receptor pathway by the dynein light chain 1

Overexpression and phosphorylation of dynein light chain 1 (DLC1) have been shown to promote the growth of breast cancer cells. However, the role of DLC1 in the action of the oestrogen receptor ( ER) remains unknown. Here, we found that oestrogen induces the transcription and expression of DLC1. DLC1 facilitated oestrogen-induced ER transactivation and anchorage-independent growth of breast cancer cells. We show that DLC1 interacts with ER, and such interaction is required for the transactivation-promoting activity of DLC1. Further, DLC1 expression led to enhanced recruitment of the DLC1-ER complex to the ER-target gene chromatin. Conversely, DLC1 down-regulation compromised the ER-transactivation activity and also its nuclear accumulation, suggesting a potential chaperone-like activity of DLC1 in the nuclear translocation of ER. Together, these data define an unexpected upregulation of DLC1 by oestrogen and a previously unrecognized DLC1-ER interaction in supporting and amplifying ER-initiated cellular responses in breast cancer cells.