Progranulin sustains STAT3 hyper-activation and oncogenic function in colorectal cancer cells

Molecular Oncology
Federica LaudisiCarmine Stolfi

Abstract

Persistent activation of Signal Transducer and Activator of Transcription (STAT)3 occurs in a high percentage of tumors, including colorectal cancer (CRC), thereby contributing to malignant cell proliferation and survival. Although STAT3 is recognized as an attractive therapeutic target in CRC, conventional approaches aimed at inhibiting its functions have met with several limitations. Moreover, the factors that sustain hyper-activation of STAT3 in CRC are not yet fully understood. The identification of tumor-specific STAT3 cofactors may facilitate the development of compounds that interfere exclusively with STAT3 activity in cancer cells. Here, we show that progranulin, a STAT3 cofactor, is upregulated in human CRC as compared to nontumor tissue/cells and its expression correlates with STAT3 activation. Progranulin physically interacts with STAT3 in CRC cells, and its knockdown with a specific antisense oligonucleotide (ASO) inhibits STAT3 activation and restrains the expression of STAT3-related oncogenic proteins, thus causing cell cycle arrest and apoptosis. Moreover, progranulin knockdown reduces STAT3 phosphorylation and cell proliferation induced by tumor-infiltrating leukocyte (TIL)-derived supernatants in CRC cell lines...Continue Reading

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Citations

Mar 1, 2020·Cell Communication and Signaling : CCS·Jia-Hui MaXia Li
Apr 19, 2021·Molecular and Cellular Biochemistry·Gayathri ChalikondaYun Suk Huh
Sep 8, 2021·Cancer Cell International·Zeynab KohandelSaeed Samarghandian

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Methods Mentioned

BETA
PCR
flow cytometry
flow
Immunoprecipitation
ELISA
antisense oligonucleotide
transfection
confocal microscopy

Software Mentioned

ZEN
LEICA
Image
Lab

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