Dataset Information

Novel tumour suppressor roles for GZMA and RASGRP1 in Theileria annulata-transformed macrophages and human B lymphoma cells.

ABSTRACT: Theileria annulata is a tick-transmitted apicomplexan parasite that infects and transforms bovine leukocytes into disseminating tumours that cause a disease called tropical theileriosis. Using comparative transcriptomics we identified genes transcriptionally perturbed during Theileria-induced leukocyte transformation. Dataset comparisons highlighted a small set of genes associated with Theileria-transformed leukocyte dissemination. The roles of Granzyme A (GZMA) and RAS guanyl-releasing protein 1 (RASGRP1) were verified by CRISPR/Cas9-mediated knockdown. Knocking down expression of GZMA and RASGRP1 in attenuated macrophages led to a regain in their dissemination in Rag2/?C mice confirming their role as dissemination suppressors in vivo. We further evaluated the roles of GZMA and RASGRP1 in human B lymphomas by comparing the transcriptome of 934 human cancer cell lines to that of Theileria-transformed bovine host cells. We confirmed dampened dissemination potential of human B lymphomas that overexpress GZMA and RASGRP1. Our results provide evidence that GZMA and RASGRP1 have a novel tumour suppressor function in both T. annulata-infected bovine host leukocytes and in human B lymphomas.

SUBMITTER: Rchiad Z

PROVIDER: S-EPMC7685166 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Novel tumour suppressor roles for GZMA and RASGRP1 in Theileria annulata-transformed macrophages and human B lymphoma cells.

Rchiad Zineb Z Haidar Malak M Ansari Hifzur Rahman HR Tajeri Shahin S Mfarrej Sara S Ben Rached Fathia F Kaushik Abhinav A Langsley Gordon G Pain Arnab A

Cellular microbiology 20200929 12

Theileria annulata is a tick-transmitted apicomplexan parasite that infects and transforms bovine leukocytes into disseminating tumours that cause a disease called tropical theileriosis. Using comparative transcriptomics we identified genes transcriptionally perturbed during Theileria-induced leukocyte transformation. Dataset comparisons highlighted a small set of genes associated with Theileria-transformed leukocyte dissemination. The roles of Granzyme A (GZMA) and RAS guanyl-releasing protein ...[more]

PMID: 32830401

Similar Datasets

Project description:Recent technical advances have broadened our understanding of processes that govern mammalian cell migration in health and disease but many of the molecular and morphological alterations that precede and accompany movement of cells - in particular in three-dimensional (3D) environments - are still incompletely understood. In this manuscript, using high-resolution and time-lapse microscopy imaging approaches, we describe morphodynamic processes during rounded/amoeboid cell invasion and molecules associated with the cellular invasion structures. We used macrophages infected with the intracellular protozoan parasite Theileria annulata, which causes Tropical Theileriosis in susceptible ruminants such as domestic cattle. T. annulata transforms its host cell that, as a result, acquires many characteristics of human cancer cells including a markedly increased potential to migrate, disseminate and expand in the body of the host animal. Hence, virulence of the disease is associated with the capability of infected cells to disseminate inside the host. Using T. annulata-transformed macrophages as a model system, we described a novel mode of rounded/amoeboid macrophage migration. We show that filopodia-like membrane extensions at the leading edge lead the way and further evolve in blebbing membrane protrusions to promote progressive expansion of the matrix. Associated with focal invasion structures we detected ezrin, radixin, moesin-family proteins and their regulatory kinase MAP4K4. Furthermore, we linked Rho-kinase activity to contractile force generation, which is essential for infected cell motility. Thus, the motility mode of these parasite-transformed macrophages contrasts with those described so far in human macrophages such as the tunneling or mesenchymal modes, which require engulfment, compaction and ingestion of matrix or proteolytic matrix degradation, respectively. Together, our data reveal protrusion dynamics at the leading edge of invading cells in 3D at unprecedented temporal and spatial resolution and suggest a novel mode of rounded/amoeboid invasive cell motility that exploits actin-driven filopodia formation in combination with pressure-driven membrane blebs.

Dataset Information

Novel tumour suppressor roles for GZMA and RASGRP1 in Theileria annulata-transformed macrophages and human B lymphoma cells.

Publications

Novel tumour suppressor roles for GZMA and RASGRP1 in Theileria annulata-transformed macrophages and human B lymphoma cells.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets