충북대학교 종양연구소에서 다음과 같이 초청세미나를 개최하오니 많은 참여 부탁드립니다.
- 다 음 -
1. 연 자 : 이 한 웅 교수 (연세대학교)
2. 일 시 : 2015년 03월 12일 (목) 오후 5시
3. 연 제 : Implication of Ei24 in autophagy and cancer
4. 장 소 : 종양연구소 세미나실 104호
5. 발 표 내 용
Etoposide-induced gene 24 (ei24/PIG8) is a recently identified p53 target gene involved in growth suppression, induction of apoptosis, autophagy, and breast cancer suppression. Based on its potential roles as a tumor suppressor gene, we have studied the physiological functions in vivo and the molecular mechanisms of Ei24. Inflammation is a critical promoter for carcinogenesis and EI24 expression was significantly reduced in human hepatocellular carcinomas (HCC), a neoplastic disease induced by chronic inflammation. In fact, Ei24+/- mice showed higher susceptibility to diethylnitrosamine (DEN)-induced tumorigenesis. Contrary to the tumor suppressive role of Ei24 in HCC, Ei24 expression was required for the progression of initiated papillomas to squamous cell carcinoma in DMBA/TPA skin carcinogenesis. We elucidated that Ei24 stabilizes PKCα by RINCK binding and degradation leading to the activation of PKCα-EGFR-STAT3 axis that is essential for the development of skin cancers. Our studies also revealed that RINCK degradation was dependent upon autophagy which is mediated by binding of Ei24 with LC3 through two LIR motifs. Besides, Ei24-mediated RINCK degradation represents a unique case of selective-macroautophagy.
Ei24/Pig8 is lost in aggressive breast tumors and thus appears to play a role in prevention of cancer metastasis. We found that loss of Ei24 promotes cancer cell metastasis in vitro and in vivo. Ei24 regulates cell-to-cell interaction and cadherin switch-mediated EMT in consequence of regulating E-cadherin. The down-regulation of EI24 showed increased motility, invasiveness, and resistance to anoikis, which accompanied by EMT process. Mechanistically, Ei24 suppresses NF-κB activity and inhibits its target genes which closely related with metastasis. We confirmed loss of Ei24 expression related to poor prognosis in human patients. Collectively, these findings demonstrate the first evidences that Ei24 contributes to cancer metastasis and is a potential prognostic marker and therapeutic target.