The components of the tumor microenvironment (TME) in solid tumors, especially chemokines, are currently attracting much attention from scientists. C-X-C motif chemokine ligand 5 (CXCL5) is one of the important chemokines in TME. Overexpression of CXCL5 is closely related to the survival time, recurrence and metastasis of cancer patients. In TME, CXCL5 binds to its receptors, such as C-X-C motif chemokine receptor 2 (CXCR2), to participate in the recruitment of immune cells and promote angiogenesis, tumor growth, and metastasis. The CXCL5/CXCR2 axis can act as a bridge between tumor cells and host cells in TME. Blocking the transmission of CXCL5/CXCR2 signals can increase the sensitivity and effectiveness of immunotherapy and slow down tumor progression. CXCL5 and CXCR2 are also regarded as biomarkers for predicting prognosis and molecular targets for customizing the treatment. In this review, we summarized the current literature regarding the biological functions and clinical significance of CXCL5/CXCR2 axis in TME. The possibility to use CXCL5 and CXCR2 as potential prognostic biomarkers and therapeutic targets in cancer is also discussed

X-linked inhibitor of apoptosis protein (XIAP) overexpression has been found to be associated with malignant cancer progression and aggression in individuals with many types of cancers. However, the molecular basis of XIAP in the regulation of cancer cell biological behavior remains largely unknown. In this study, we found that a deficiency of XIAP expression in human cancer cells by either knock-out or knockdown leads to a marked reduction in ␤-actin polymerization and cytoskeleton formation. Consistently, cell migration and invasion were also decreased in XIAP-deficient cells compared with parental wildtype cells. Subsequent studies demonstrated that the regulation of cell motility by XIAP depends on its interaction with the Rho GDP dissociation inhibitor (RhoGDI) via the XIAP RING domain. Furthermore, XIAP was found to negatively regulate RhoGDI SUMOylation, which might affect its activity in controlling cell motility. Collectively, our studies provide novel insights into the molecular mechanisms by which XIAP regulates cancer invasion and offer a further theoretical basis for setting XIAP as a potential prognostic marker and specific target for treatment of cancers with metastatic properties.The X-linked inhibitor of apoptosis protein (XIAP) 3 is a member of the IAP family that has received substantial attention during the last few years. Biochemical and structural studies have indicated that XIAP has three zinc-binding baculovirus IAP repeat (BIR) domains (BIR1-3), a loop region, and a RING finger (1). The BIR3 domain of XIAP is able to bind and inhibit caspase-9, whereas the BIR2 region binds and inhibits active caspase-3 and caspase-7. The RING domain of XIAP has E3 ligase activity and is able to degrade proteins by linking them to ubiquitin molecules (2-4). More recently, XIAP has been found to be a regulator of the cell cycle through binding the cell cycle regulators MAGED1 and NRAGE and to play an important role in the control of intracellular copper levels through ubiquitin ligase-dependent regulation of the copper-regulating gene MURR1 (5, 6). The ability of XIAP to regulate these pathways, uncoupled with its caspase inhibitory activities, indicates its distinct properties and functions. Based on the finding that XIAP-deficient mice do not display obvious apoptotic phenotypes (7), it was hypothesized that there might be new functions and signaling pathways affected by XIAP, which are probably distinct from those involved in apoptotic caspase cascades.There is growing evidence showing the correlation between high XIAP overexpression and malignant cancer aggression (8, 9). Comparison of XIAP expression between adjacent malignant tissue and normal tissue invariably demonstrates that XIAP is much more highly expressed in the malignant cancer tissue (10 -20). Poorly differentiated carcinomas also display significantly higher levels of XIAP expression than do well differentiated carcinomas (13,(17)(18)(19)(20). Moreover, XIAP expression in metastatic specimens is much higher than that in primary cancers ...

The binding of uropathogenic Escherichia coli to the urothelial surface is a crucial initial event for establishing urinary tract infection because it allows the bacteria to gain a foothold on the urothelial surface, thus preventing them from being removed by micturition. In addition, it triggers bacterial invasion as well as host urothelial defense. This binding is mediated by the FimH adhesin located at the tip of the bacterial type 1-fimbrium, a filamentous attachment apparatus, and its urothelial receptor. We have prepared a biotinylated, recombinant FimH-FimC adhesin:chaperone complex and used it to identify its mouse urothelial receptor. The FimH-FimC complex binds specifically to a single 24 kDa major mouse urothelial plaque protein, which we identified as uroplakin Ia by mass spectrometry, cDNA cloning and immunoreactivity. The terminal mannosyl moieties on Asn-169 of uroplakin Ia are responsible for FimH as well as concanavalin A binding. Although FimH binds to uroplakin Ia with only moderate strength (Kd ∼100 nM between pH 4 and 9), the binding between multiple fimbriae of a bacterium and the crystalline array of polymerized uroplakin receptors should achieve high avidity and stable bacterial attachment. The FimH-FimC complex binds preferentially to the mouse urothelial umbrella cells in a pattern similar to uroplakin staining. Our results indicate that the structurally related uroplakins Ia and Ib are glycosylated differently, that uroplakin Ia serves as the urothelial receptor for the type 1-fimbriated E. coli, and that the binding of uropathogenic bacteria to uroplakin Ia may play a key role in mediating the urothelial responses to bacterial attachment.

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