Roles of CXCL5 on migration and invasion of liver cancer cells

Xu, Xiaojing; Huang, Peixin; Yang, Biwei; Wang, Xiangdong; Xia, Jinglin

doi:10.1186/1479-5876-12-193

Cited by 27 publications

(30 citation statements)

References 33 publications

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“…In liver cancer, CXCL5 was reported to be a candidate of diagnostic and therapeutic biomarkers with potential clinical values . Meanwhile, CXCL5 could also attract neutrophil toward melanoma and HCC . Therefore, CXCL5 affects the complex tumor microenvironment at multiple ways.…”

Section: Discussionmentioning

confidence: 92%

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Cancer‐associated fibroblasts promote PD‐L1 expression in mice cancer cells via secreting CXCL5

Zhou

Zhang

et al. 2019

Intl Journal of Cancer

146

131

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Cancer‐associated fibroblasts (CAFs) play a key role in orchestrating the tumor malignant biological properties within tumor microenvironment and evidences demonstrate that CAFs are a critical regulator of tumoral immunosuppression of the T cell response. However, the functions and regulation of CAFs in the expression of programmed death‐ligand 1 (PD‐L1) in melanoma and colorectal carcinoma (CRC) are not completely understood. Herein, by scrutinizing the expression of α‐SMA and PD‐L1 in melanoma and CRC tissues, we found that CAFs was positive correlated with PD‐L1 expression. Further analyses showed that CAFs promoted PD‐L1 expression in mice tumor cells. By detecting a majority of cytokines expression in normal mice fibroblasts and CAFs, we determined that CXCL5 was abnormal high expression in CAFs and the immunohistochemistry and in situ hybridization confirmed that were CAFs which were expressing CXCL5. In addition, CXCL5 promoted PD‐L1 expression in B16, CT26, A375 and HCT116. The silencing of CXCR2, the receptor of CXCL5, inhibited the PD‐L1 expression induced by CAFs in turn. Functionally, CXCL5 derived by CAFs promoted PD‐L1 expression in mice tumor cells through activating PI3K/AKT signaling. LY294002, the inhibitor of PI3K, confirmed that CXCL5 forested an immunosuppression microenvironment by promoting PD‐L1 expression via PI3K/AKT signaling. Meanwhile, the B16/CT26 xenograft tumor models were used and both CXCR2 and p‐AKT were found to be positively correlated with PD‐L1 in the xenograft tumor tissues. The immunosuppressive action of CAFs on tumor cells is probably reflective of them being a potential therapeutic biomarker for melanoma and CRC.

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Section: Discussionmentioning

confidence: 92%

“…29 Meanwhile, CXCL5 could also attract neutrophil toward melanoma and HCC. 25,30 Therefore, CXCL5 affects the complex tumor microenvironment at multiple ways. In our research, CXCL5 inhibited antitumor immunity via PD-L1 through activating PI3K and AKT signaling in melanoma and CRC cells.…”

Section: Discussionmentioning

confidence: 99%

Cancer‐associated fibroblasts promote PD‐L1 expression in mice cancer cells via secreting CXCL5

Zhou

Zhang

et al. 2019

Intl Journal of Cancer

146

131

View full text Add to dashboard Cite

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“…; Xu et al . ). Two recent reports have showed that miR‐31 promotes hyperproliferation of keratinocytes and suppresses generation of peripherally derived regulatory T cells and that loss of miR‐31 reduces severity of psoriasis and experimental autoimmune encephalomyelitis (Yan et al .…”

Section: Discussionmentioning

confidence: 97%

“…In addition, CCL17 serves as a chemoattractant for regulatory T cells in tumor microenvironment (Mishalian et al 2014). Furthermore, CXCL5, CX3CL1, IL-6 and Angptl2 function as mediators of local, chronic inflammation and cancer progression (Borsig et al 2014;Kadomatsu et al 2014;Xu et al 2014). Two recent reports have showed that miR-31 promotes hyperproliferation of keratinocytes and suppresses generation of peripherally derived regulatory T cells and that loss of miR-31 reduces severity of psoriasis and experimental autoimmune encephalomyelitis (Yan et al 2015;Zhang et al 2015a).…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‐31 is a positive modulator of endothelial–mesenchymal transition and associated secretory phenotype induced by TGF‐β

et al. 2015

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Transforming growth factor‐β (TGF‐β) plays central roles in endothelial–mesenchymal transition (EndMT) involved in development and pathogenesis. Although EndMT and epithelial–mesenchymal transition are similar processes, roles of microRNAs in EndMT are largely unknown. Here, we report that constitutively active microRNA‐31 (miR‐31) is a positive regulator of TGF‐β‐induced EndMT. Although the expression is not induced by TGF‐β, miR‐31 is required for induction of mesenchymal genes including α‐SMA, actin reorganization and MRTF‐A activation during EndMT. We identified VAV3, a regulator of actin remodeling and MRTF‐A activity, as a miR‐31 target. Global transcriptome analysis further showed that miR‐31 positively regulates EndMT‐associated unique secretory phenotype (EndMT‐SP) characterized by induction of multiple inflammatory chemokines and cytokines including CCL17, CX3CL1, CXCL16, IL‐6 and Angptl2. As a mechanism for this phenomenon, TGF‐β and miR‐31 suppress Stk40, a negative regulator of NF‐κB pathway. Interestingly, TGF‐β induces alternative polyadenylation (APA)‐coupled miR‐31‐dependent Stk40 suppression without concomitant miR‐31 induction, and APA‐mediated exclusion of internal poly(A) sequence in Stk40 3′UTR enhances target efficiency of Stk40. Finally, miR‐31 functions as a molecular hub to integrate TGF‐β and TNF‐α signaling to enhance EndMT. These data confirm that constitutively active microRNAs, as well as inducible microRNAs, serve as phenotypic modifiers interconnected with transcriptome dynamics during EndMT.

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“…Gastric tumors exhibit increased CX3CL1 expression [47], and the CX3CR1 receptor is highly expressed in association with more advanced stages. Xu et al [48] and Yang et al [49] published results of another chemokine (CXCL5) in liver cancer, with data also indicating an oncogenic role.…”

Section: Discussionmentioning

confidence: 99%

Mutational burden of hepatoblastomas: a role for the CX3CL1/CX3CR1 chemokine signaling pathway

Costa

et al. 2019

Preprint

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Background: Hepatoblastoma is an embryonal liver tumor supposed to arise from the impairment of hepatocyte differentiation during embryogenesis. CTNNB1 is the only recurrently mutated gene, and this relative paucity of somatic mutations poses a challenge to risk stratification and development of targeted therapies. Methods: In this study, we investigated by exome sequencing the burden of somatic mutations in a cohort of 10 hepatoblastomas, including a congenital case. Results: Our data disclosed a low mutational background with only three recurrently mutated genes: CTNNB1 and two novel candidates, CX3CL1 and CEP164. The major finding was a recurrent mutation (A235G) identified in two hepatoblastomas at the CX3CL1 gene; evaluation of RNA and protein expression revealed up-regulation of CX3CL1 in tumors. The analysis was replicated in two independents cohorts, substantiating that an activation of the CX3CL1/CX3CR1 pathway occurs in hepatoblastomas, with a predominance of these proteins in the cytoplasm of tumor cells. These proteins were not detected in the infiltrated lymphocytes of inflammatory regions of the tumors, in which they should be expressed in normal conditions, whereas necrotic regions exhibited negative tumor cells, but strongly positive infiltrated lymphocytes. Our data suggested that CX3CL1/CX3CR1 upregulation may be a common feature of hepatoblastomas, potentially related to chemotherapy response and progression. In addition, three mutational signatures were identified in hepatoblastomas, two of them with predominance of either the COSMIC signatures 1 and 6, found in all cancer types, or the COSMIC signature 29, related only with tobacco chewing habit; a third novel mutational signature presented an unspecific pattern with an increase of C>A mutations. Conclusions: Overall, we present here evidence that CX3CL1/CX3CR1 chemokine signaling pathway is likely involved with hepatoblastoma tumorigenesis or progression, besides reporting a novel mutational signature specific to a hepatoblastoma subset.

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Roles of CXCL5 on migration and invasion of liver cancer cells

Cited by 27 publications

References 33 publications

Cancer‐associated fibroblasts promote PD‐L1 expression in mice cancer cells via secreting CXCL5

Cancer‐associated fibroblasts promote PD‐L1 expression in mice cancer cells via secreting CXCL5

MicroRNA‐31 is a positive modulator of endothelial–mesenchymal transition and associated secretory phenotype induced by TGF‐β

Mutational burden of hepatoblastomas: a role for the CX3CL1/CX3CR1 chemokine signaling pathway

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