Search

Background:Members of the integrin β superfamily(ITGBs) have been shown to be aberrantly expressed in various human cancers and involved in tumorigenesis and progression. However, the diverse expression patterns and prognostic values of the entire ITGB family members in gastric cancer(GC) has not been systematically investigated.Methods:In the current study, Oncomine, GEPIA, Kaplan Meier plotter, TIMER, GeneMANIA, STRING and Metascape database were employed to explore the transcriptional and survival data of ITGB superfamily members in GC. Moreover, we confirmed the mRNA expression levels of ITGB superfamily members in GC cell lines by qRT-PCR.Results:The mRNA expression level of ITGB1/2/4/5/8 was upregulated in GC, while the expression level of ITGB7 was downregulated. Higher expression of ITGB2/7 was significantly associated with the tumor stage of patients with GC. However, we found that the expression level of ITGB1/2/4/5/6/7/8 was remarkably increased in GC cell lines compared to stomach normal cell lines, while ITGB3 expression was decreased in the former than in the latter. Meanwhile,higher expression levels of ITGB2/6/7 were closely correlated with better overall clinical survival (OS) and recurrence-free survival (RFS) in GC patients, while higher ITGB3/4/5 expression were strongly associated with poorer OS and RFS.We also discovered that the functions of ITGBs and their adjacent genes are mainly related to protein complexes involved in cell adhesion. the functions of ITGBs and their adjacent proteins are mainly related to focal adhesion, cell adhesion molecules, proteoglycans in cancer, small cell lung cancer, rap1 signaling pathway, IgA production by intestinal immune network, and microRNAs in cancer.In addition, the expression of ITGBs was significantly correlated with the infiltration of multiple immune cells, including B cells, CD8+ T cells, CD4+ T cells, neutrophils, macrophages, and dendritic cells.Conclusions:Our results suggested that abnormal expression of ITGBs plays a key role in the progression of GC and that ITGBs may be potential prognostic biomarkers and therapeutic targets for GC.

Retinoic acid (RA) analogs have been used in the treatment of a variety of cancers; however, their application is limited due to serious therapy-related sequelae. In the present study, the effects of a novel RA analog, 4-amino-2-trifluoromethyl-phenyl retinate (ATPR), on the growth of gastric cancer cells were evaluated. Three gastric cancer cell lines, AGS, MKN-74 and SC-M1, were treated with either all‑trans retinoic acid (ATRA) or ATPR, and their growth and distribution in different cell cycle phases were assessed using an MTT assay and propidium iodide (PI) staining followed by flow cytometry. The binding affinity of ATPR to the retinoic acid receptors, retinoic acid receptor-α (RAR-α) and retinoid X receptor-α (RXR-α), was determined using ligand-binding assays. Activator protein-1 (AP-1) activity was measured using a luciferase reporter assay. Western blot analysis was used to determine cyclin E, Bcl-2 and Bax protein expression. ATPR preferentially bound RXR-α (0.04 nM) as compared with RAR-α (20.96 nM). Although both ATRA and ATPR inhibited the growth of AGS, MKN-74 and SC-M1 cells in a dose-dependent manner, a significantly greater inhibitory effect was observed with treatment with 5 and 500 µM ATPR for 3 days (P

Orai1 is one of the key components of store-operated Ca(2+) entry (SOCE) involved in diverse physiological functions. Orai1 may associate with other proteins to form a signaling complex. In the present study, we investigated the interaction between Orai1 and small conductance Ca(2+)-activated potassium channel 3 (SK3). With the use of RNA interference technique, we found that the SOCE and its associated membrane hyperpolarization were reduced while Orai1 was knocked down by a specific Orai1 siRNA in guinea pig gallbladder smooth muscle. However, with the use of isometric tension measurements, our results revealed that agonist-induced muscle contractility was significantly enhanced after Orai1 protein was knocked down or the tissue was treated by SK3 inhibitor apamin, but not affected by larger conductance Ca(2+)-activated potassium channel inhibitor iberiotoxin or intermediate conductance Ca(2+)-activated potassium channel inhibitor TRAM-34. In addition, in the presence of apamin, Orai1 siRNA had no additional effect on agonist-induced contraction. In coimmunoprecipitation experiment, SK3 and Orai1 pulled down each other. These data suggest that, Orai1 physically associated with SK3 to form a signaling complex in gallbladder smooth muscle. Ca(2+) entry via Orai1 activates SK3, resulting in membrane hyperpolarization in gallbladder smooth muscle. This hyperpolarizing effect of Orai1-SK3 coupling could serve to prevent excessive contraction of gallbladder smooth muscle in response to contractile agonists.