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Establishment of cell polarity across cell types and organisms involves distinct mechanisms that follow a common pattern: first a polarity cue arises, followed by asymmetric organization executed by polarity proteins. Loss of cell polarity has a key role in cancer development. The MACF1 gene, Microtubule actin cross-linking factor 1, or MACF1, a cytoskeletal protein is involved in oocyte development, cell proliferation, and cell migration. In addition to these roles, MACF1 is linked to metastatic invasion leading to tumor progression in numerous human cancers including gynecological cancers of endometrial and ovarian cancer. Given the functional importance of cell polarity, here we provide computational evidence of MACF1 in gynecological cancers. The comparison of multi-omic data for patient tumor and normal cells facilitates the understanding of the molecular mechanisms that contribute to tumor cell proliferation, abnormal cell adhesion and cell migration. Leveraging the rich datasets hosted by the NCI-funded ISB-Cancer Genomics Cloud, we performed a cloud-based patient cohort analysis across diverse multi-omics datasets. We quantified differential gene expression profiles from patients in the cohort as well as identified somatic mutation differences. The most common genomic alteration for MACF1 was the in-frame mutation. Genomic alterations and mutations were aligned to functional domains of the MACF1 protein to determine both frequency and spatial distribution. Gene-gene expression correlation analyses identified statistically significant correlations between MACF1 and other well-known cancer driver genes. Together, using a data driven cloud-computing approach we gain novel insights into the role of MACF1 regulation of cell polarity in the progression of cancer.

Alignment of Cysu with Drosophila orthologs. The highly conserved peroxidase region indicated by the consensus line appears in red, uppercase letters; a weak conservation is indicated in lowercase blue. Drosophila species are highly conserved (~95%) among the following: D. grimshawi (DGRIM), D. mojavensis (DMOJA), D. virilis (DVIRI), D. willistoni (DWILL), D. pseudoobscura (DPSEU), D. ananassae (DANAN), D. erecta (DEREC), D. yakuba (DYAKU), D. sechellia (DSECH), and D. simulans (DSIMU), D. persimilis (DPERS). The green line indicates the peroxinectin region. Figure S2. Severity of Cysu phenotype changes with time. Flies were collected (Day 1) photographed at different time interval until Day 2. In all cases the phenotype gets more and more severe indicating that the entire wing was affected. Figure S3. Knockdown of Cysu expression in each essential compartment of the wing disc cause no effect on wing development because adult wings develop normally. Except for Actin-GALâ >â CysuIR where ubiquitous suppression results in collapsed wing effect. (PPT 17161 kb)

Background Thus far, a handful of genes have been shown to be related to the wing maturation process in insects. A novel heme peroxidase enzyme known as curly suppressor (Cysu)(formerly CG5873), have been characterized in this report because it is involved in wing morphogenesis. Using bioinformatics tools we found that Cysu is remarkably conserved in the genus Drosophila (>95%) as well as in invertebrates (>70%), although its vertebrate orthologs show poor homology. Time-lapse imaging and histochemical analyses have confirmed that the defective wing phenotype of Cysu is not a result of any underlying cellular alterations; instead, its wings fail to expand in mature adults. Results The precise requirement of Cysu in wings was established by identifying a bona fide mutant of Cysu from the Bloomington Drosophila Stock Centre collection. Its requirement in the wing has also been shown by RNA knockdown of the gene. Subsequent transgenic rescue of the mutant wing phenotype with the wild-type gene confirmed the phenotype resulting from Cysu mutant. With appropriate GAL4 driver like engrailed-GAL4, the Cysu phenotype was compartmentalized, which raises a strong possibility that Cysu is not localized in the extracellular matrix (ECM); hence, Cysu is not engaged in bonding the dorsal and ventral cuticular layers. Finally, shortened lifespan of the Cysu mutant suggests it is functionally essential for other biological processes as well. Conclusion Cysu, a peroxinectin-like gene, is required during the wing maturation process in Drosophila because as a heme peroxidase, Cysu is capable of utilizing H2O2, which plays an essential role in post-eclosion wing morphogenesis. Electronic supplementary material The online version of this article (doi:10.1186/s12861-016-0143-8) contains supplementary material, which is available to authorized users.