Tying the knot between cytokine and toll-like receptor signaling in gastrointestinal tract cancers

Yuet Mei Hazel Tye, Brendan John Jenkins

Research output: Contribution to journalArticleResearchpeer-review

20 Citations (Scopus)

Abstract

Inflammation-associated malignancies of the gastrointestinal tract (GI), including those of the stomach and colon, collectively rank as the highest cause of cancer-related deaths worldwide. It has been well documented that the deregulated activation of the archetypal pro-inflammatory and oncogenic transcription factors nuclear factor-kappa B (NF-kappaB) and signal transducer and activator of transcription (STAT)3 is a common feature of GI cancers that invariably correlates with poor prognosis. Signal transducer and activator of transcription 3 and NF-kappaB are key downstream signal transducers of the interleukin (IL)-6 cytokine and toll-like receptor (TLR) families, respectively, and until recently, the potential involvement of these two families in the pathogenesis of cancer has been investigated in isolation. However, there is now emerging evidence of the complex interplay between the IL-6 cytokine and TLR families in GI tract cancers, with a surprising twist in the identification of a non-immune role for specific TLR family members. In this review, we discuss the molecular mechanisms associated with cross-talk between the IL-6 cytokine family/STAT3 signaling network and the TLR family/NF-kappaB signaling network, and we address the potential benefit of their therapeutic targeting in gastric and colorectal cancers.
Original languageEnglish
Pages (from-to)1139 - 1145
Number of pages7
JournalCancer Science
Volume104
Issue number9
DOIs
Publication statusPublished - 2013

Cite this

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abstract = "Inflammation-associated malignancies of the gastrointestinal tract (GI), including those of the stomach and colon, collectively rank as the highest cause of cancer-related deaths worldwide. It has been well documented that the deregulated activation of the archetypal pro-inflammatory and oncogenic transcription factors nuclear factor-kappa B (NF-kappaB) and signal transducer and activator of transcription (STAT)3 is a common feature of GI cancers that invariably correlates with poor prognosis. Signal transducer and activator of transcription 3 and NF-kappaB are key downstream signal transducers of the interleukin (IL)-6 cytokine and toll-like receptor (TLR) families, respectively, and until recently, the potential involvement of these two families in the pathogenesis of cancer has been investigated in isolation. However, there is now emerging evidence of the complex interplay between the IL-6 cytokine and TLR families in GI tract cancers, with a surprising twist in the identification of a non-immune role for specific TLR family members. In this review, we discuss the molecular mechanisms associated with cross-talk between the IL-6 cytokine family/STAT3 signaling network and the TLR family/NF-kappaB signaling network, and we address the potential benefit of their therapeutic targeting in gastric and colorectal cancers.",
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Tying the knot between cytokine and toll-like receptor signaling in gastrointestinal tract cancers. / Tye, Yuet Mei Hazel; Jenkins, Brendan John.

In: Cancer Science, Vol. 104, No. 9, 2013, p. 1139 - 1145.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Tye, Yuet Mei Hazel

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AB - Inflammation-associated malignancies of the gastrointestinal tract (GI), including those of the stomach and colon, collectively rank as the highest cause of cancer-related deaths worldwide. It has been well documented that the deregulated activation of the archetypal pro-inflammatory and oncogenic transcription factors nuclear factor-kappa B (NF-kappaB) and signal transducer and activator of transcription (STAT)3 is a common feature of GI cancers that invariably correlates with poor prognosis. Signal transducer and activator of transcription 3 and NF-kappaB are key downstream signal transducers of the interleukin (IL)-6 cytokine and toll-like receptor (TLR) families, respectively, and until recently, the potential involvement of these two families in the pathogenesis of cancer has been investigated in isolation. However, there is now emerging evidence of the complex interplay between the IL-6 cytokine and TLR families in GI tract cancers, with a surprising twist in the identification of a non-immune role for specific TLR family members. In this review, we discuss the molecular mechanisms associated with cross-talk between the IL-6 cytokine family/STAT3 signaling network and the TLR family/NF-kappaB signaling network, and we address the potential benefit of their therapeutic targeting in gastric and colorectal cancers.

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