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Inflammation-induce...
Inflammation-induced PELP1 expression promotes tumorigenesis by activating GM-CSF paracrine secretion in the tumor microenvironment
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- Vuttaradhi, Veena Kumari (författare)
- Indian Institute of Technology Madras
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- Ezhil, Inemai (författare)
- Indian Institute of Technology Madras
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- Ramani, Divya (författare)
- Indian Institute of Technology Madras,Sri Ramachandra University
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- Kanumuri, Rahul (författare)
- Sri Ramachandra University,Indian Institute of Technology Madras
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- Raghavan, Swetha (författare)
- Indian Institute of Technology Madras
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- Balasubramanian, Vaishnavi (författare)
- Sri Ramachandra University
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- Saravanan, Roshni (författare)
- Sri Ramachandra University
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- Kanakarajan, Archana (författare)
- Sri Ramachandra University
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- Joseph, Leena Dennis (författare)
- Sri Ramachandra University
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- Pitani, Ravi Shankar (författare)
- Sri Ramachandra University
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- Sundaram, Sandhya (författare)
- Sri Ramachandra University
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- Sjölander, Anita (författare)
- Lund 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
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- Venkatraman, Ganesh (författare)
- Sri Ramachandra University
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- Rayala, Suresh Kumar (författare)
- Indian Institute of Technology Madras
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(creator_code:org_t)
- Elsevier BV, 2022
- 2022
- Engelska.
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Ingår i: Journal of Biological Chemistry. - : Elsevier BV. - 0021-9258. ; 298:1
- Relaterad länk:
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http://dx.doi.org/10... (free)
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http://www.jbc.org/a...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
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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
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
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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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