Loss of interleukin-17 receptor D promotes chronic inflammation-associated tumorigenesis

Girondel, Charlotte; Lévesque, Kim; Langlois, Marie‐Josée; Pasquin, Sarah; Saba-El-Leil, Marc K.; Rivard, Nathalie; Friesel, Robert; Servant, Marc J.; Gauchat, Jean‐François; Lesage, Sylvie; Meloche, Sylvain

doi:10.1038/s41388-020-01540-4

Cited by 21 publications

(17 citation statements)

References 43 publications

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“…Interrogation of the TCGA and GTEx databases also revealed that expression of IL-17RD mRNA is lower in colon adenocarcinomas as compared to adjacent tissue and normal intestinal mucosa. IL17RD is significantly downregulated in the microsatellite instability subgroup of colorectal cancer patients (38). These observations are consistent with the hypothesis of a tumor suppressor function of IL-17RD.…”

Section: Il-17rd Is Down-regulated In a Variety Of Human Cancerssupporting

confidence: 89%

“…Given the multiple in vitro studies documenting the antagonistic effect of IL-17RD on mitogenic signaling pathways and cell proliferation, it is tempting to speculate that the protein may exert its tumor suppressor function by curtailing cancer cell proliferation. Surprisingly, we did not observe any difference in the number of phospho-ERK1/ 2 and Ki-67 positive cells between wild type and Il17rd -/colon tumors in the AOM-DSS model (38). Similarly, we failed to detect changes in ERK1/2 phosphorylation and cell proliferation in the intestinal epithelium of Il17rd -/mice as compared to control animals.…”

Section: Il-17rd Limits Tumor-associated Inflammation Without Affecticontrasting

confidence: 72%

“…The authors determined that the SEFIR domain of IL-17RD interacts with the TIR domain of the adaptor protein MyD88 to block TLR downstream signaling. In a recent study, we provided additional evidence that IL-17RD negatively regulates TLR as well as IL-17A signaling in epithelial cells ( 38 ). Importantly, we found that genetic inactivation of Il17rd markedly exacerbates the inflammatory response in a model of colitis-associated cancer, illustrated by a strong enrichment in inflammation-related gene signatures in colon tumors and elevated expression of pro-inflammatory cytokines ( 38 ).…”

Section: Il-17rd Is a Regulator Of Receptor Tyrosine Kinase And Innatmentioning

confidence: 91%

“…We also found that depletion of IL-17RD by siRNAs did not affect the proliferation rate of human colon carcinoma HCT 116 cells and modestly reduced proliferation of murine MC-38 cells. Thus, we concluded that IL-17RD deficiency alone has no significant impact on the proliferation of normal or transformed intestinal cells (38). Interestingly, systematic analysis of IL-17RD dependency using the publicly available depmap portal (https://depmap.org/portal/depmap/) revealed that no single cancer cell line shows a dependency on IL-17RD expression for their proliferation (Figure 2).…”

Section: Il-17rd Limits Tumor-associated Inflammation Without Affectimentioning

confidence: 92%

“…To directly address the role of endogenous IL-17RD in tumorigenesis, we have analyzed a longitudinal cohort of wild type, heterozygous and homozygous Il17rd mutant mice. We found that deficiency of IL-17RD leads to the formation of spontaneous tumors in aging mice in a gene dosage-dependent manner ( 38 ). Histological analysis revealed the presence of tumors in the lungs, female reproductive organs, lymphoid organs and gastrointestinal tract.…”

Section: Role Of Il-17rd In Tumorigenesismentioning

confidence: 99%

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Interleukin-17 Receptor D in Physiology, Inflammation and Cancer

Girondel

Meloche

2021

Front. Oncol.

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Interleukin-17 receptor D (IL-17RD) is an evolutionarily conserved member of the IL-17 receptor family. Originally identified as a negative regulator of fibroblast growth factor (FGF) signaling under the name of Sef (Similar expression to FGF genes), IL-17RD was subsequently reported to regulate other receptor tyrosine kinase signaling pathways. In addition, recent studies have shown that IL-17RD also modulates IL-17 and Toll-like receptor (TLR) signaling. Combined genetic and cell biology studies have implicated IL-17RD in the control of cell proliferation and differentiation, cell survival, lineage specification, and inflammation. Accumulating evidence also suggest a role for IL-17RD in tumorigenesis. Expression of IL-17RD is down-regulated in various human cancers and recent work has shown that loss of IL-17RD promotes tumor formation in mice. However, the exact mechanisms underlying the tumor suppressor function of IL-17RD remain unclear and some studies have proposed that IL-17RD may exert pro-tumorigenic effects in certain contexts. Here, we provide an overview of the signaling functions of IL-17RD and review the evidence for its involvement in cancer.

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Section: Il-17rd Is Down-regulated In a Variety Of Human Cancerssupporting

confidence: 89%

Section: Il-17rd Limits Tumor-associated Inflammation Without Affecticontrasting

confidence: 72%

Section: Il-17rd Is a Regulator Of Receptor Tyrosine Kinase And Innatmentioning

confidence: 91%

Section: Il-17rd Limits Tumor-associated Inflammation Without Affectimentioning

confidence: 92%

Section: Role Of Il-17rd In Tumorigenesismentioning

confidence: 99%

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Interleukin-17 Receptor D in Physiology, Inflammation and Cancer

Girondel

Meloche

2021

Front. Oncol.

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In‐depth analysis of the relationship between bovine intestinal organoids and enteroids based on morphology and transcriptome

Zhang

Yan

et al. 2022

J Tissue Eng Regen Med

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Intestinal organoids and enteroids as excellent models are miniaturized and simplified for studying intestinal physiological and pathological functions, drug screening, and regenerative medicine. Recently, the application demands for organoids and enteroids in organ development and nutrition metabolism, immune and cancer research increased. But there are few comparative studies on both of them, especially in immunity and metabolism, which is also conducive to further clarifying the role of crypt stem cells and stromal cells. In our study, “natural” organoids were obtained by tissue culture from fetal bovine jejunum and enteroids were successfully isolated and cultured from organoids without supplementing exogenous factors and Matrigel. These mini‐guts displayed similar features to the intestine through immunohistochemistry and transmission electron microscopy. Organoid and enteroid were systematically compared based on the transcriptome. And some of the results were verified by qRT‐PCR. Our results showed KDGs (Key driver genes) (e.g., SLC13A1, HOXA7, HOXA6, HOXA5, and HOXD4) of organoids enriched in signaling pathways related to organ development and morphology and metabolism. KDGs (e.g., IL‐6, PTGS2, CDH1, JUN, and EGFR) of enteroid were involved in cancer, MAPK, and immune‐related signaling pathways. To the Wnt signaling pathway, highly expressed genes in organoids, including RSPO2, NOTUM, WNT6, and RSPO3, supported the homeostasis of crypt stem cells. Enteroids highly expressed CTNNB1 and WNTs. In addition, we found that organoids and enteroids carried out different functions in immunity and metabolism due to different cell compositions. Therefore, it suggested organoid is more compatible and comprehensive, and enteroid is qualified for the research of immunity and cancer.

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