RelA

A tale of a stitch in time

Murray Korc

Research output: Contribution to journalReview article

1 Citation (Scopus)

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a deadly cancer in which NF-κB pathways promote biological aggressiveness. In this issue of the JCI, Lesina et al. investigated the role of RelA, the p65 partner of p50 that together form the most common NF-κB complex, in the early stages of pancreatic malignant transformation and in established PDAC. By deleting Rela in the context of an oncogenic Kras-driven autochthonous model of PDAC, the authors demonstrated that RelA is a mediator of oncogeneinduced senescence (OIS) and the senescence-associated secretory phenotype (SASP) that attenuates acinar-to-ductal metaplasia, pancreatic intraepithelial neoplasia (PanIN) formation, and PanIN progression to PDAC. Loss of the tumor-suppressor function of RelA in the early stages of Krasdriven pancreatic neoplastic transformation was associated with decreased OIS and SASP and a protumorigenic tumor microenvironment that harbored more M2 macrophages and myeloid-derived suppressor cells. The beneficial effects of RelA were mediated by increased expression of CXCL1 and its activation of CXCR2. By contrast, in advanced stages of Kras-driven murine PDAC, loss of p53 or p16 was associated with senescence bypass, and RelA deficiency in this context attenuated cancer cell proliferation and prolonged mouse survival, indicating that RelA enhances tumor progression in established PDAC.

Original languageEnglish (US)
Pages (from-to)2799-2801
Number of pages3
JournalJournal of Clinical Investigation
Volume126
Issue number8
DOIs
StatePublished - Aug 1 2016

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Adenocarcinoma
Neoplasms
Phenotype
Tumor Microenvironment
Metaplasia
Macrophages
Cell Proliferation

ASJC Scopus subject areas

  • Medicine(all)

Cite this

RelA : A tale of a stitch in time. / Korc, Murray.

In: Journal of Clinical Investigation, Vol. 126, No. 8, 01.08.2016, p. 2799-2801.

Research output: Contribution to journalReview article

Korc, Murray. / RelA : A tale of a stitch in time. In: Journal of Clinical Investigation. 2016 ; Vol. 126, No. 8. pp. 2799-2801.
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