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NIH Research Festival

September 13 – 15, 2017

Integrated melanoma/melanoblast transcriptomics identifies novel metastasis regulators: A role for ER stress

Wednesday, September 13, 2017 – Poster Session II
3:30 – 5:00 p.m.

FAES Terrace

NCI

DIR-9

Authors

  • KL Marie
  • AM Michalowski
  • HT Michael
  • T Guo
  • YC Tsai
  • AM Weissman
  • HH Yang
  • MP Lee
  • MR Zaidi
  • E Pérez-Guijarro
  • A Sassano
  • C-P Day
  • H Arnheiter
  • S Davis
  • PS Meltzer
  • PJ Mishra
  • G Merlino

Abstract

Cutaneous malignant melanoma is often highly aggressive, metastatic, and resistant to current therapeutic approaches. Since the behavior of metastatic melanoma cells can phenocopy that of embryonic melanoblasts, we here employed a whole genome transcriptomic approach to test if melanoma’s penchant for metastasis can be attributed to broad re-initiation of pathways otherwise restricted predominantly to embryos. We used a genetically engineered mouse designed to fluorescently label melanocytic cells to purify developmentally-staged melanoblasts and generate rich datasets of their transcriptomes. We demonstrate that these datasets represent discrete subgroups of metastatic melanoma patients, and can be used to produce a gene signature that serves as a biomarker predicting patient survival. Functional studies confirmed that expression of melanoblast-specific genes can enhance mouse and human melanoma metastasis, including the poorly characterized retrotransport chaperone KDELR3, highlighting the importance of Endoplasmic Reticulum homeostasis in metastasis. We link KDELR3 with the E3 ubiquitin-protein ligase gp78, through which it helps to regulate both mitochondrial metabolism and stability of the metastasis suppressor, KAI1. Our work identifies a metastasis-development axis, providing novel insights into mechanisms of melanoma progression, and a source of untested pathways for treating metastatic melanoma.

Scientific Focus Area: Institute, Center, and Scientific Directors

This page was last updated on Friday, March 26, 2021

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2017 program

Download the 2017 Research Festival Schedule Overview (6 pages)

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Current Research Festival

  • 2021
  • 2019
    • General Schedule of Events
    • Plenary Sessions
    • Poster Session
    • Data Blitz
    • FARE Award Ceremony
    • Special Exhibits on Resources for Intramural Research
    • Technical Sales Association (TSA) Research Festival Exhibit Tent Show
    • Research Festival Committee
  • 2018
    • General Schedule of Events
    • Plenary Sessions
    • Concurrent Symposia Sessions
    • Poster Sessions
    • FARE Award Ceremony
    • Special Exhibits on Resources for Intramural Research
    • Technical Sales Association (TSA) Research Festival Exhibit Tent Show
    • Research Festival Committees
  • 2017
    • General Schedule of Events
    • Plenary Sessions
    • Concurrent Symposia Sessions
    • Poster Sessions
    • FARE Award Ceremony
    • Future Research Leaders
    • Special Exhibits on Resources for Intramural Research
    • Technical Sales Association (TSA) Research Festival Exhibit Tent Show
    • Research Festival Committees
  • 2016
    • General Schedule of Events
    • Plenary Sessions
    • Concurrent Symposia Sessions
    • Poster Sessions
    • Browse by Presenter Name
    • Browse by Presenter IC
    • FARE Award Ceremony
    • Future Research Leaders
    • Special Exhibits on Resources for Intramural Research
    • Technical Sales Association (TSA) Research Festival Exhibit Tent Show
    • Tours of the National Library of Medicine and Clinical Center
    • Research Festival Committees
  • 2015
    • General Schedule of Events
    • Plenary Sessions
    • Concurrent Workshop Sessions
    • Poster Sessions
    • Browse by Presenter Name
    • Browse by Presenter IC
    • FARE Award Ceremony
    • Future Research Leaders
    • Special Exhibits on Resources for Intramural Research
    • TSA Research Festival Exhibit Show
    • NIH Tours
    • Research Festival Committees
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