Abstract 4608: RRBP1 overexpression is frequently found In lung cancer patients and alleviates intracellular stress induced apoptosis through positive regulation of GRP78 in lung cancer
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Medientyp:
E-Artikel
Titel:
Abstract 4608: RRBP1 overexpression is frequently found In lung cancer patients and alleviates intracellular stress induced apoptosis through positive regulation of GRP78 in lung cancer
Beteiligte:
Tsai, Hong-Yuan;
Hsiao, Michael
Erschienen:
American Association for Cancer Research (AACR), 2012
Beschreibung:
<jats:title>Abstract</jats:title>
<jats:p>How tumors evade apoptotic signals and survive during cancer progression has not yet been resolved. To unravel the molecular mechanisms involved in lung carcinogenesis will greatly improve therapy. Endoplasmic reticulum is a cellular organelle in which secretory and proteins are synthesized and modified. These processes are always enhanced in cancer cells. Ribosome binding protein1(RRBP1) was originally reported as a ribosome-binding protein on the rough endoplasmic reticulum. In this report, we showed that RRBP1 was highly expressed in the early stage of lung cancer compared to their adjunct normal tissue samples by utilizing lung cancer tissue array(n=87). Depletion of RRBP1 by short-hairpin RNAs significantly reduced cell growth and induced apoptosis in A549 and CL1-5 cells, but not in normal lung cells(BEAS2B). Furthermore, RRBP1-depleted NSCLC cells could activate CD95/caspase signaling pathways. Treatment with caspase8 inhibitor (ZVAD-FMK) or with shRNA against caspase8 was sufficient to suppress apoptosis in RRBP1-depleted cells. This effect is associated with significantly reduction in the expression of GRP78. GRP78, an antiapoptotic protein widely upregulated in cancer, plays a critical role in chemotherapy resistance in some cancers. According to our data, ectopic expression of RRBP1 alleviated tunicamycin induced apoptosis by upregulation GRP78 protein level in lung cancer cells. A strong correlation was observed between the expression of RRBP1 and GRP78 in tumor biopsies from NSCLC patients, supporting the concept that GRP78 expression levels are controlled by RRBP1. Taken together, this study not only showed that GRP78 is regulated by RRBP1 but also report that RRBP1 and GRP78 expression is involved in NSCLC growth and progression. suggest that RRBP1 is required for lung cancer growth and development, which may be a useful target in lung cancer treatment and expected to provide the basis for a rational approach for the development of new molecular targeted therapies</jats:p>
<jats:p>Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4608. doi:1538-7445.AM2012-4608</jats:p>