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A conserved major facilitator superfamily member orchestrates a subset of O-glycosylation to aid macrophage tissue invasion.

eLife | 2019

Aberrant display of the truncated core1 O-glycan T-antigen is a common feature of human cancer cells that correlates with metastasis. Here we show that T-antigen in Drosophila melanogaster macrophages is involved in their developmentally programmed tissue invasion. Higher macrophage T-antigen levels require an atypical major facilitator superfamily (MFS) member that we named Minerva which enables macrophage dissemination and invasion. We characterize for the first time the T and Tn glycoform O-glycoproteome of the Drosophila melanogaster embryo, and determine that Minerva increases the presence of T-antigen on proteins in pathways previously linked to cancer, most strongly on the sulfhydryl oxidase Qsox1 which we show is required for macrophage tissue entry. Minerva's vertebrate ortholog, MFSD1, rescues the minerva mutant's migration and T-antigen glycosylation defects. We thus identify a key conserved regulator that orchestrates O-glycosylation on a protein subset to activate a program governing migration steps important for both development and cancer metastasis.

Pubmed ID: 30910009 RIS Download

Research resources used in this publication

Associated grants

  • Agency: NIH HHS, United States
    Id: P40 OD018537
  • Agency: NIH HHS, United States
    Id: P40 OD010949
  • Agency: H2020 Marie SkÅ‚odowska-Curie Actions, International
    Id: CIG 334077/IRTIM
  • Agency: Austrian Science Fund, International
    Id: DASI_FWF01_P29638S
  • Agency: Danish National Research Foundation, International
    Id: DNRF107
  • Agency: H2020 Marie SkÅ‚odowska-Curie Actions, International
    Id: IIF GA-2012-32950 BB: DICJI

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

This is a list of tools and resources that we have found mentioned in this publication.


ATCC (tool)

RRID:SCR_001672

Global nonprofit biological resource center (BRC) and research organization that provides biological products, technical services and educational programs to private industry, government and academic organizations. Its mission is to acquire, authenticate, preserve, develop and distribute biological materials, information, technology, intellectual property and standards for the advancement and application of scientific knowledge. The primary purpose of ATCC is to use its resources and experience as a BRC to become the world leader in standard biological reference materials management, intellectual property resource management and translational research as applied to biomaterial development, standardization and certification. ATCC characterizes cell lines, bacteria, viruses, fungi and protozoa, as well as develops and evaluates assays and techniques for validating research resources and preserving and distributing biological materials to the public and private sector research communities.

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RRID:SCR_002037

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RRID:SCR_002380

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QIAGEN (tool)

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Program to Reduce Incontinence by Diet and Exercise (tool)

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Randomized controlled trial being conducted at two clinical centers in the United States to learn more about the effects of weight loss on urinary incontinence. About 330 overweight women aged 30 or older will participate and will be followed for 18 months. Efficacy of weight reduction as a treatment for urinary incontinence will be examined at 6 months following the intensive weight control program, and the sustained impact of the intervention will be examined at 18 months. To increase the maintenance of weight reduction and facilitate evaluation of the enduring impact of weight loss on urinary incontinence, they propose to study a motivation-based weight maintenance program. At the end of the intensive weight control program, women randomized to the weight loss program will be randomized to either a 12-month skill-based maintenance intervention or to a motivation-based maintenance intervention. The maintenance interventions maximize the potential for sustained weight loss and will allow them to determine if long-term weight reduction will produce continued improvement in urinary incontinence.

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y[1] w[*]; P{w[+mC]=srp.Hemo-GAL4}2, P{w[+mC]=UAS-GFP.U}3 (tool)

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w[1118]; Df(3L)BSC117/TM6B, Tb[1] (tool)

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RRID:CVCL_4358

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RRID:SCR_002845

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RRID:CVCL_0125

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RRID:SCR_006457

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RRID:BDSC_17262

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RRID:SCR_008410

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RRID:SCR_004431

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RRID:SCR_012931

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RRID:SCR_000821

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RRID:SCR_002845

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RRID:SCR_013805

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RRID:SCR_006457

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