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Striatin is a novel modulator of cell adhesion.

ABSTRACT: The adherens junctions (AJs) and tight junctions (TJs) provide critical adhesive contacts between neighboring epithelial cells and are crucial for epithelial adhesion, integrity, and barrier functions in a wide variety of tissues and organisms. The striatin protein family, which are part of the striatin interaction phosphatases and kinases complex, are multidomain scaffolding proteins that play important biologic roles. We have previously shown that striatin colocalizes with the tumor suppressor protein adenomatous polyposis coli in the TJs of epithelial cells. Here we show that striatin affects junction integrity and cell migration, probably through a mechanism that involves the adhesion molecule E-cadherin. Cells engaged in cell-cell adhesion expressed a high MW-modified form of striatin that forms stable associations with detergent-insoluble, membrane-bound cellular fractions. In addition, striatin has recently been suggested to be a target of the poly (ADP-ribose) polymerases Tankyrase 1, and we have found that striatin interacts with Tankyrase 1 and is subsequently poly-ADP-ribosylated. Taken together, our results suggest that striatin is a novel cell-cell junctional protein that functions to maintain correct cell adhesion and may have a role in establishing the relationship between AJs and TJs that is fundamental for epithelial cell-cell adhesion.-Lahav-Ariel, L., Caspi, M., Nadar-Ponniah, P. T., Zelikson, N., Hofmann, I., Hanson, K. K., Franke, W. W., Sklan, E. H., Avraham, K. B., Rosin-Arbesfeld, R. Striatin is a novel modulator of cell adhesion.

SUBMITTER: Lahav-Ariel L

PROVIDER: S-EPMC6988865 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Striatin is a novel modulator of cell adhesion.

Lahav-Ariel Lital L Caspi Michal M Nadar-Ponniah Prathamesh T PT Zelikson Natalie N Hofmann Ilse I Hanson Kirsten K KK Franke Werner W WW Sklan Ella H EH Avraham Karen B KB Rosin-Arbesfeld Rina R

FASEB journal : official publication of the Federation of American Societies for Experimental Biology 20181228 4

The adherens junctions (AJs) and tight junctions (TJs) provide critical adhesive contacts between neighboring epithelial cells and are crucial for epithelial adhesion, integrity, and barrier functions in a wide variety of tissues and organisms. The striatin protein family, which are part of the striatin interaction phosphatases and kinases complex, are multidomain scaffolding proteins that play important biologic roles. We have previously shown that striatin colocalizes with the tumor suppressor ...[more]

PMID: 30592649

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Project description:BackgroundThe view of prostate cancer (PCa) progression as a result of the interaction of epithelial cancer cells with the host's immune system is supported by the presence of tumor infiltrating lymphocytes (TILs). TILs fate and interaction with the tumor microenvironment is mediated by accessory molecules such as CD5 and CD6, two signal-transducing coreceptors involved in fine-tuning of T cell responses. While the nature of the CD5 ligand is still controversial, CD6 binds CD166/ALCAM, a cell adhesion molecule involved in progression and dissemination of epithelial cancers, including PCa. The purpose of the present study was to determine the role of CD5, CD6, and CD166/ALCAM gene variants in PCa.MethodsFunctionally relevant CD5 (rs2241002 and rs2229177), CD6 (rs17824933, rs11230563, and rs12360861) and CD166/ALCAM (rs6437585, rs579565, rs1044243, and rs35271455) single nucleotide polymorphisms (SNPs) were genotyped in germline DNA samples from 376 PCa patients. Their association with PCa prognostic factors, namely biochemical recurrence (BCR) and International Society of Urological Pathology (ISUP) grade was analyzed by generalized linear models and survival analyses.ResultProportional hazards regression showed that the minor CD6 rs12360861AA and CD166/ALCAM rs579565AA genotypes were associated with earlier BCR, with hazard ratios of 2.65 (95% CI: 1.39-5.05, p = 0.003) and 1.86, (95% CI: 1.02-3.39, p = 0.043), respectively. Individually, none of the analyzed SNPs was significantly associated with ISUP grade, but haplotype analyses revealed association of the CD5 rs2241002C -rs2229177T haplotype with ISUP grade ≥2, with odds ratio of 1.52 (95% CI: 1.05-2.21, p = 0.026).ConclusionThe results show the impact on PCa aggressiveness and recurrence brought about by gene variants involved in modulation of lymphocyte activation (CD5, CD6) and immune-epithelial cell adhesion (CD166/ALCAM) in PCa aggressiveness and recurrence, thus supporting a role for host immune response in PCa pathophysiology.

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Striatin is a novel modulator of cell adhesion.

Publications

Striatin is a novel modulator of cell adhesion.

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