TRIP-Br1 oncoprotein inhibits autophagy, apoptosis, and necroptosis under nutrient/serum-deprived condition

Abstract

TRIP-Br1 oncogenic protein has been shown to have multiple biological functions in cells. In this study, we demonstrate that TRIP-Br1 functions as an oncoprotein by inhibiting autophagy, apoptosis, and necroptosis of cancer cells and eventually helping them to survive under the nutrient/serum starved condition. TRIP-Br1 expression level was significantly increased in conditions with low levels of nutrients. Nutrient depleted conditions were induced by culturing cancer cells until they were overcrowded with high cell density or in media deprived of glucose, amino acids, or serum. Among them, serum starvation significantly enhanced the expression of TRIP-Br1 only in all tested breast cancer cell lines (MCF7, MDA-MB-231, T47D, MDA-MB-435, Hs578D, BT549, and MDA-MB-435) but not in the three normal cell lines (MCF10A, HfCH8, and NIH3T3). As compared with the control cells, the introduction of TRIP-Br1 silencing siRNA into MCF7 and MDA-MB-231 cells accelerated cell death by inducing apoptosis and necroptosis. In this process, TRIP-Br1 confers resistance to serum starvation-induced cell deaths by stabilizing the XIAP protein and inhibiting cellular ROS production. Moreover, our data also show that the intracellular increase of TRIP-Br1 protein resulting from serum starvation seems to occur in part through the blockage of PI3K/AKT signaling pathway.

Δ2-Troglitazone promotes cytostatic rather than pro-apoptotic effects in breast cancer cells cultured in high serum conditions

“…For instance, some members of the transcriptional regulator interacting with the PHD-bromodomain (TRIP-Br) family were reported to be involved in such phenomenon. 38,39 One might suggest that D2-TGZ could disturb the molecular mechanisms responsible for this protection against apoptosis.…”

Identification of appropriate housekeeping genes for quantitative RT-PCR analysis in MDA-MB-231 and NCI-H460 human cancer cell lines under hypoxia and serum deprivation

“…In the hypoxic microenvironment, cancer cells activate major adaptive pathways, including a shift towards anaerobic metabolism and a significant reprogramming of the cell transcriptional activity as a survival strategy [27]. Cancer cell cultures grown under serum deprivation conditions is commonly used to mimic the tumor milieu, where due to the lack of sufficient vascularization, cancer cells are inefficiently supplied with neither oxygen nor nutrients [18,19]. Furthermore, serum availability has been recently associated with altered expression of HKG [11].…”

“…Since hypoxia and serum deprivation are conditions that resemble the context of the in vivo tumor microenvironment [18,19], we decided herein to investigate the best HKG combination for transcript level analysis under these conditions. For this purpose, we analyzed the expression stability of five commonly used HKGs (ACTB, β 2M, GUSB, 18S rRNA and PPIA) in mammary and pulmonary tumor cell line models.…”

Microarray Analysis of Differentially Expressed Profiles of Circular RNAs in a Mouse Model of Intestinal Ischemia/Reperfusion Injury with and Without Ischemic Postconditioning

“…Notably, although none of the four circRNA-miRNA-mRNA pathways have been reported previously, several molecules were found to be involved in certain pathophysiological processes when separately analyzed. For example, Sertad1 (also known as Sei-1 or TRIP-Br1) is able to inhibit ROS-or nutrient/ serum deprivation-induced apoptosis in cancer cells [45,46], while Jam2 belongs to the junctional adhesion molecule (JAM) family and is involved in the formation of tight junctions in both endothelial and epithelial cells [47,48]. Recently, Zhong et al predicted a circTCF25-miR-103a-3p/miR-107-CDK6 pathway in bladder cancer by multiple bioinformatical approaches.…”