PCAF interacts with XBP-1S and mediates XBP-1S-dependent transcription

Lew, Qiao Jing; Chu, Kai Ling; Lee, Jialing; Koh, Poh Ling; Rajasegaran, Vikneswari; Teo, Jin Yuan; Chao, Sheng-Hao

The tumor microenvironment is hypoglycemic and hypoxic, resulting in induction of UPR and overexpression of XBP-1. Recent studies show the involvement of XBP-1 in tumorigenesis of various cancers and suggest XBP-1 as a potential target for anti-cancer therapeutics (10) (11) (12) 43) . Fujimoto et al. investigated the expression of XBP-1 in 11 primary breast cancers and five breast cancer cell lines, including MCF7. The increased expression of XBP-1 was detected in all breast cancers and cell lines examined, but not in the non-cancerous breast issue (44) . In addition, clinical results showed that high levels of XBP-1S increased the survival of breast cancers (45) . Our data presented here demonstrate the functional importance of PCAF in mediating the expression of XBP-1S target genes in MCF7 cells (Figures 6 and 7) , suggesting a potential role of PCAF in XBP-1S-mediated tumerigenesis of breast cancers. Furthermore, PCAF may be an essential factor for other XBP-1S-mediated signaling pathways. For example, XBP-1S is one of the key components in the transcriptional program controlling plasma cell differentiation (1) . It would be worthwhile to examine the importance of PCAF-XBP-1S during the development of plasma cells.