Ghanekar, Y. | bioRxiv Science

bioRxiv2022

Regenerating aggregates of hydra display unique cytoskeletal organisation that is absent in a regeneration-deficient strain

Hydra has the unique ability to regenerate from aggregates of dissociated single cells that lack positional information. We compared two strains of hydra, a strain of hydra that was capable of regenerating from aggregates and a strain of hydra that was deficient in this type of regeneration. We observed unique actin cytoskeletal arrangements that were present in the regenerates of regeneration-competent strain but not in the regeneration-deficient strain. Concomitantly, the regeneration-deficient strain failed to organise the extracellular cytoskeleton of laminin and collagen between ectodermal and endodermal epithelial cells. These interesting preliminary observations highlight the importance of the cytoskeletal organisation in regeneration of hydra and suggest that regeneration from the aggregates of dissociated cells through de novo patterning requires correct structural organisation of cytoskeletal elements.

zoology↗

bioRxiv2018

In Silico Analysis Reveals a Shared Immune Signature in CASP8-Mutated Carcinomas with Varying Correlations to Prognosis.

BackgroundSequencing studies across multiple cancers continue to reveal the spectrum of mutations and genes involved in the pathobiology of these cancers. Exome sequencing of oral cancers, a subset of Head and Neck Squamous cell Carcinomas (HNSCs) common among tobacco-chewing populations, revealed that ~34% of the affected patients harbor mutations in the CASP8 gene. Uterine Corpus Endometrial Carcinoma (UCEC) is another cancer type where about 10% cases harbor CASP8 mutations. Caspase-8, the protease encoded by CASP8 gene, plays a dual role in programmed cell death, which in turn has an important role in tumor cell death and drug resistance. CASP8 is a protease required for the extrinsic pathway of apoptosis and is also a negative regulator of necroptosis. Using bioinformatics approaches to mine data in The Cancer Genome Atlas, we compared the molecular features and survival of these carcinomas with and without CASP8 mutations.\n\nResultsOur in silico analyses showed that HNSCs with CASP8 mutations displayed a prominent signature of genes involved in immune response and inflammation, and were rich in immune cell infiltrates. However, in contrast to Human Papilloma Virus-positive HNSCs, a subtype that exhibits high immune cell infiltration and better overall survival, HNSC patients with mutant-CASP8 tumors did not display any survival advantage. A similar bioinformatic analyses in UCECs revealed that while UCECs with CASP8 mutations also displayed an immune signature, they had better overall survival, in contrast to the HNSC scenario. On further examination, we found that there was significant up-regulation of neutrophils as well as the cytokine, IL33 in mutant-CASP8 HNSCs, both of which were not observed in mutant-CASP8 UCECs.\n\nConclusionsThese results suggested that carcinomas with mutant CASP8 have broadly similar immune signatures albeit with different effects on survival. We hypothesize that subtle tissue-dependent differences could influence survival by modifying the micro-environment of mutant-CASP8 carcinomas. High neutrophil numbers, which is a well-known negative prognosticator in HNSCs, and/or high IL33 levels may be some of the factors affecting survival of mutant-CASP8 cases.

cancer biology↗