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Inflammation-induce...
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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 ...
Nummerbeteckningar
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LIBRIS-ID:oai:lup.lub.lu.se:f6a06aaa-47ba-4e9e-8ef1-5b77345fd6a4
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https://lup.lub.lu.se/record/f6a06aaa-47ba-4e9e-8ef1-5b77345fd6a4URI
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https://doi.org/10.1016/j.jbc.2021.101406DOI
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Språk:engelska
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Sammanfattning på:engelska
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Ämneskategori:art swepub-publicationtype
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Ämneskategori:ref swepub-contenttype
Anmärkningar
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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 ...)
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Ezhil, InemaiIndian Institute of Technology Madras
(författare)
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Ramani, DivyaIndian Institute of Technology Madras,Sri Ramachandra University
(författare)
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Kanumuri, RahulSri Ramachandra University,Indian Institute of Technology Madras
(författare)
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Raghavan, SwethaIndian Institute of Technology Madras
(författare)
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Balasubramanian, VaishnaviSri Ramachandra University
(författare)
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Saravanan, RoshniSri Ramachandra University
(författare)
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Kanakarajan, ArchanaSri Ramachandra University
(författare)
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Joseph, Leena DennisSri Ramachandra University
(författare)
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Pitani, Ravi ShankarSri Ramachandra University
(författare)
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Sundaram, SandhyaSri Ramachandra University
(författare)
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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)
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Venkatraman, GaneshSri Ramachandra University
(författare)
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Rayala, Suresh KumarIndian Institute of Technology Madras
(författare)
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Indian Institute of Technology MadrasSri Ramachandra University
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Journal of Biological Chemistry: Elsevier BV298:10021-9258
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Vuttaradhi, Veen ...
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Ezhil, Inemai
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Ramani, Divya
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Kanumuri, Rahul
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Raghavan, Swetha
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Balasubramanian, ...
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Saravanan, Roshn ...
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Kanakarajan, Arc ...
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Joseph, Leena De ...
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Pitani, Ravi Sha ...
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Sundaram, Sandhy ...
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Sjölander, Anita
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Venkatraman, Gan ...
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Rayala, Suresh K ...
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