The role and clinical significance of the CXCL17-CXCR8 (GPR35) axis in breast cancer

Guo, Ya; Zhou, Yujie; Yang, Xiao; Shao, Zhi Min; Ou, Zhou Luo

doi:10.1016/j.bbrc.2017.09.113

Cited by 45 publications

(58 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the case of the Gα 13 G.H5.23 Leu374‐Ile mutation, our study suggests this is linked to reduced function in response to GPR35 activation, and it will be interesting to explore if this is also the case for other Gα 13 ‐interacting receptors. GPR35 has been reported to be up‐regulated in breast cancer tissue compared with normal adjacent tissue (54), but the overall significance of this remains uncertain.…”

Section: Discussionmentioning

confidence: 99%

Receptor selectivity between the G proteins Gα ₁₂ and Gα ₁₃ is defined by a single leucine‐to‐isoleucine variation

et al. 2019

View full text Add to dashboard Cite

Despite recent advances in structural definition of GPCR–G protein complexes, the basis of receptor selectivity between G proteins remains unclear. The Gα 12 and Gα 13 subtypes together form the least studied group of heterotrimeric G proteins. G protein–coupled receptor 35 (GPR35) has been suggested to couple efficiently to Gα 13 but weakly to Gα 12 . Using combinations of cells genome-edited to not express G proteins and bioluminescence resonance energy transfer–based sensors, we confirmed marked selectivity of GPR35 for Gα 13 . Incorporating Gα 12 /Gα 13 chimeras and individual residue swap mutations into these sensors defined that selectivity between Gα 13 and Gα 12 was imbued largely by a single leucine-to-isoleucine variation at position G.H5.23. Indeed, leucine could not be substituted by other amino acids in Gα 13 without almost complete loss of GPR35 coupling. The critical importance of leucine at G.H5.23 for GPR35–G protein interaction was further demonstrated by introduction of this leucine into Gα q , resulting in the gain of coupling to GPR35. These studies demonstrate that Gα 13 is markedly the most effective G protein for interaction with GPR35 and that selection between Gα 13 and Gα 12 is dictated largely by a single conservative amino acid variation.—Mackenzie, A. E., Quon, T., Lin, L.-C., Hauser, A. S., Jenkins, L., Inoue, A., Tobin, A. B., Gloriam, D. E., Hudson, B. D., Milligan, G. Receptor selectivity between the G proteins Gα 12 and Gα 13 is defined by a single leucine-to-isoleucine variation.

show abstract

Section: Discussionmentioning

confidence: 99%

Receptor selectivity between the G proteins Gα ₁₂ and Gα ₁₃ is defined by a single leucine‐to‐isoleucine variation

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Both GPR35a and GPR35b are functionally active. 11,12 Studies at the mRNA level reveal that GPR35 is expressed at highest levels in small intestine followed by stomach; colon; rectum; and in some abdominal, myeloid and lymphoid cancer cell lines. 10,[13][14][15] In this study, we investigated whether determination of GRP35 levels in lymph nodes of colon cancer (CC) patients will be of value for predicting the formation of distant metastasis.…”

Section: Introductionmentioning

confidence: 99%

Utility of G protein-coupled receptor 35 expression for predicting outcome in colon cancer

et al. 2019

View full text Add to dashboard Cite

The utility of mRNA and protein determinations of G protein-coupled receptor 35, that is, GPR35a (GPR35 V1) and GPR35b (GPR35 V2/3), as indicators of outcome for colon cancer patients after curative surgery was investigated. Expression levels of V1 and V2/3 GPR35, carcinoembryonic antigen and CXCL17 mRNAs were assessed in primary tumours and regional lymph nodes of 121 colon cancer patients (stage I–IV), colon cancer cell lines and control colon epithelial cells using real-time quantitative reverse transcriptase-polymerase chain reaction. Expression of G protein-coupled receptor 35 was investigated by two-colour immunohistochemistry and immunomorphometry. GPR35 V2/3 mRNA, but not V1 mRNA, was expressed in colon cancer cell lines, primary colon tumours and control colon epithelial cells. Haematoxylin and eosin positive (H&E(+)), but not H&E(–), lymph nodes expressed high levels of GPR35 V2/3 mRNA ( P<0.0001). GPR35b and carcinoembryonic antigen proteins were simultaneously expressed in many colon cancer tumour cells. Kaplan–Meier and hazard ratio analysis revealed that patients with lymph nodes expressing high levels of GPR35 V2/3 mRNA and, in particular, in the group of patients with lymph nodes also expressing carcinoembryonic antigen mRNA, had a short disease-free survival time, 67 months versus 122 months at 12-year follow-up (difference: 55 months, P = 0.001; hazard ratio: 3.6, P = 0.002). In conclusion, high level expression of G protein-coupled receptor 35 V2/3 mRNA in regional lymph nodes of colon cancer patients is a sign of poor prognosis.

show abstract

“…Several groups have associated the expression of CXCL17 with tumor development, because tumor cells overexpressing CXCL17 induce bigger tumors and grow faster when implanted in mice . Several groups have reported that expression of Cxcl17 is up‐regulated in several cancers including esophageal, lung, breast, endometrium, liver, and pancreas, and CXCL17 expression correlates with poor survival and prognosis …”

Section: Introductionmentioning

confidence: 99%

“…Accordingly, GPR35 is expressed by CXCL17‐responsive cells like macrophages and dendritic cells. GPR35 is also expressed in some breast cancer cell lines that respond to CXCL17 . However, another receptor likely exists because GPR35 does not appear to be the receptor through which CXCL17 signals in THP‐1 cells …”

Section: Introductionmentioning

confidence: 99%

“…GPR35 is also expressed in some breast cancer cell lines that respond to CXCL17. 15 However, another receptor likely exists because GPR35 does not appear to be the receptor through which CXCL17 signals in THP-1 cells. 23 A recent report described that CXCL17 attenuates inflammation in a mouse psoriasis model through the recruitment of myeloid derived suppressor cells that can, in turn, recruit regulatory T cells (Tregs).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Cxcl17 -/- mice develop exacerbated disease in a T cell-dependent autoimmune model

Hernández‐Ruiz

Othy

Herrera

et al. 2019

Journal of Leukocyte Biology

View full text Add to dashboard Cite

CXCL17 is a homeostatic chemokine in the mucosa known to chemoattract dendritic cells and macrophages but can also be expressed elsewhere under inflammatory conditions. Cxcl17−/− mice have lower numbers of macrophages or dendritic cells in mucosal tissues. CXCL17 is also able to chemoattract suppressor myeloid cells that can recruit regulatory T cells. To explore a possible role of Cxcl17 in T cells, we studied T cell populations from Cxcl17−/− or wild‐type (WT) littermate mice. Cxcl17−/− mice have higher numbers of CD4+ and CD8+ T cells in spleen and lymph nodes (LNs). Upon activation, they produce higher levels of several proinflammatory cytokines and chemokines. Furthermore, a Cxcl17−/− mouse developed exacerbated disease in a T cell‐dependent model of experimental autoimmune encephalomyelitis (EAE). By 18 days after immunization with myelin oligodendrocyte peptide, only 44% of Cxcl17−/− mice were still alive vs. 90% for WT mice. During EAE, Cxcl17−/− mice exhibited higher numbers of lymphoid and myeloid cells in spleen and LNs, whereas they had less myeloid cell infiltration in the CNS. Cxcl17−/− mice also had higher levels of some inflammatory cytokines in serum, suggesting that they may be involved in the poor survival of these mice. Abnormal T cell function may reflect altered myeloid cell migration, or it could be due to altered T cell development in the thymus. We conclude that CXCL17 is a novel factor regulating T cell homeostasis and function.

show abstract

The role and clinical significance of the CXCL17-CXCR8 (GPR35) axis in breast cancer

Cited by 45 publications

References 18 publications

Receptor selectivity between the G proteins Gα ₁₂ and Gα ₁₃ is defined by a single leucine‐to‐isoleucine variation

Receptor selectivity between the G proteins Gα ₁₂ and Gα ₁₃ is defined by a single leucine‐to‐isoleucine variation

Utility of G protein-coupled receptor 35 expression for predicting outcome in colon cancer

Cxcl17 -/- mice develop exacerbated disease in a T cell-dependent autoimmune model

Contact Info

Product

Resources

About

The role and clinical significance of the CXCL17-CXCR8 (GPR35) axis in breast cancer

Cited by 45 publications

References 18 publications

Receptor selectivity between the G proteins Gα 12 and Gα 13 is defined by a single leucine‐to‐isoleucine variation

Receptor selectivity between the G proteins Gα 12 and Gα 13 is defined by a single leucine‐to‐isoleucine variation

Utility of G protein-coupled receptor 35 expression for predicting outcome in colon cancer

Cxcl17 -/- mice develop exacerbated disease in a T cell-dependent autoimmune model

Contact Info

Product

Resources

About

Receptor selectivity between the G proteins Gα ₁₂ and Gα ₁₃ is defined by a single leucine‐to‐isoleucine variation

Receptor selectivity between the G proteins Gα ₁₂ and Gα ₁₃ is defined by a single leucine‐to‐isoleucine variation