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Sökning: id:"swepub:oai:lup.lub.lu.se:f6a06aaa-47ba-4e9e-8ef1-5b77345fd6a4" > Inflammation-induce...

  • Vuttaradhi, Veena KumariIndian Institute of Technology Madras (författare)

Inflammation-induced PELP1 expression promotes tumorigenesis by activating GM-CSF paracrine secretion in the tumor microenvironment

  • Artikel/kapitelEngelska2022

Förlag, utgivningsår, omfång ...

  • Elsevier BV,2022

Nummerbeteckningar

  • LIBRIS-ID:oai:lup.lub.lu.se:f6a06aaa-47ba-4e9e-8ef1-5b77345fd6a4
  • https://lup.lub.lu.se/record/f6a06aaa-47ba-4e9e-8ef1-5b77345fd6a4URI
  • https://doi.org/10.1016/j.jbc.2021.101406DOI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

Ingår i deldatabas

Klassifikation

  • Ämneskategori:art swepub-publicationtype
  • Ämneskategori:ref swepub-contenttype

Anmärkningar

  • The inflammatory tumor microenvironment has been implicated as a major player fueling tumor progression and an enabling characteristic of cancer, proline, glutamic acid, and leucine-rich protein 1 (PELP1) is a novel nuclear receptor coregulator that signals across diverse signaling networks, and its expression is altered in several cancers. However, investigations to find the role of PELP1 in inflammation-driven oncogenesis are limited. Molecular studies here, utilizing macrophage cell lines and animal models upon stimulation with lipopolysaccharide (LPS) or necrotic cells, showed that PELP1 is an inflammation-inducible gene. Studies on the PELP1 promoter and its mutant identified potential binding of c-Rel, an NF-κB transcription factor subunit, to PELP1 promoter upon LPS stimulation in macrophages. Recruitment of c-Rel onto the PELP1 promoter was validated by chromatin immunoprecipitation, further confirming LPS mediated PELP1 expression through c-Rel–specific transcriptional regulation. Macrophages that overexpress PELP1 induces granulocyte–macrophage colony-stimulating factor secretion, which mediates cancer progression in a paracrine manner. Results from preclinical studies with normal–inflammatory–tumor progression models demonstrated a progressive increase in the PELP1 expression, supporting this link between inflammation and cancer. In addition, animal studies demonstrated the connection of PELP1 in inflammation-directed cancer progression. Taken together, our findings provide the first report on c-Rel–specific transcriptional regulation of PELP1 in inflammation and possible granulocyte–macrophage colony-stimulating factor–mediated transformation potential of activated macrophages on epithelial cells in the inflammatory tumor microenvironment, reiterating the link between PELP1 and inflammation-induced oncogenesis. Understanding the regulatory mechanisms of PELP1 may help in designing better therapeutics to cure various inflammation-associated malignancies.

Ämnesord och genrebeteckningar

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Ezhil, InemaiIndian Institute of Technology Madras (författare)
  • Ramani, DivyaIndian Institute of Technology Madras,Sri Ramachandra University (författare)
  • Kanumuri, RahulSri Ramachandra University,Indian Institute of Technology Madras (författare)
  • Raghavan, SwethaIndian Institute of Technology Madras (författare)
  • Balasubramanian, VaishnaviSri Ramachandra University (författare)
  • Saravanan, RoshniSri Ramachandra University (författare)
  • Kanakarajan, ArchanaSri Ramachandra University (författare)
  • Joseph, Leena DennisSri Ramachandra University (författare)
  • Pitani, Ravi ShankarSri Ramachandra University (författare)
  • Sundaram, SandhyaSri Ramachandra University (författare)
  • Sjölander, AnitaLund University,Lunds universitet,Cellpatologi, Malmö,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Cell Pathology, Malmö,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Skåne University Hospital(Swepub:lu)expp-asj (författare)
  • Venkatraman, GaneshSri Ramachandra University (författare)
  • Rayala, Suresh KumarIndian Institute of Technology Madras (författare)
  • Indian Institute of Technology MadrasSri Ramachandra University (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:Journal of Biological Chemistry: Elsevier BV298:10021-9258

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