LRIG2 is a growth suppressor of Hec-1A and Ishikawa endometrial adenocarcinoma cells by regulating PI3K/AKT- and EGFR-mediated apoptosis and cell-cycleopen access
- Authors
- Suh, Dae-Shik; Park, Si Eun; Jin, Hanyong; Lee, Kangseok; Bae, Jeehyeon
- Issue Date
- Jan-2018
- Publisher
- NATURE PUBLISHING GROUP
- Citation
- ONCOGENESIS, v.7, no.1
- Journal Title
- ONCOGENESIS
- Volume
- 7
- Number
- 1
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/1426
- DOI
- 10.1038/s41389-017-0019-1
- ISSN
- 2157-9024
- Abstract
- Although endometrial cancer is the most common type of gynecological malignancy in developed countries, its molecular etiology is not well understood. Leucine-rich repeat and immunoglobulin-like domain 2 (LRIG2) is an evolutionarily conserved gene, but its functions in the endometrium are unknown. In this study, we found that LRIG2 is highly downregulated in endometrial adenocarcinoma patients and that it functions as a tumor suppressor. LRIG2 induced the mitochondrion-mediated apoptotic pathways by regulating stoichiometric balance among BCL-2 family proteins, whereby pro-survival members, MCL-1 and BCL-xL, were downregulated and pro-apoptotic BAK and BAX were upregulated. LRIG2 also inhibited proliferation of the Hec-1A and Ishikawa endometrial adenocarcinoma cells by upregulating p21. LRIG2 induced BAX and BAK dependent cell death that was efficiently prevented by MCL 1 overexpression. Furthermore, we found that LRIG2 unexpectedly phosphor-activates phosphoinositide 3-kinase (PI3K)/AKT and epidermal growth factor receptor (EGFR), which are conventionally accepted as survival signaling cues in diverse types of cancer. We observed that PI3K/AKT and EGFR serve as key kinases that have roles as growth suppressors of Hec-1A endometrial cancer cells by mediating the LRIG2-induced modulation of the BCL-2 family of proteins and p21. In vivo delivery of antisense DNAs against LRIG2 promoted the Hec-1A endometrial tumor growth in a xenograft mouse model, and immunoblotting of these tumor extracts showed consistent modulation of AKT, EGFR, the BCL-2 family members, and p21. Thus, our results demonstrated that LRIG2 is a growth suppressor of endometrial adenocarcinoma cells.
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Collections - College of Pharmacy > School of Pharmacy > 1. Journal Articles
- College of Natural Sciences > Department of Life Science > 1. Journal Articles
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