A S100A14-CCL2/CXCL5 signaling axis drives breast cancer metastasis

Li, Xukun; Wang, Minjie; Gong, Tongyang; Lei, Xuemeng; Hu, Ting; Tian, Maoqing; Ding, Fang; Ma, Fei; Chen, Hongyan; Liu, Zhihua

doi:10.7150/thno.42087

Cited by 44 publications

(31 citation statements)

References 45 publications

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“…In this study, the translocation of NF-κB from the cytoplasm to the nucleus promoted by NLRP7 enhanced the binding of NF-κB to the CCL2 promoter, thereby increasing its expression and secretion. Previous studies showed that the genes encoding CCL2 are downstream targets of the NF-κB transcription factor, which are crucial for cancer progression and metastasis [ 25 , 49 ]. Therefore, the NF-κB-CCL2 signaling axis plays a critical role in the effect of NLRP7 on promoting TAM polarization and CRC progression.…”

Section: Discussionmentioning

confidence: 99%

NLRP7 deubiquitination by USP10 promotes tumor progression and tumor-associated macrophage polarization in colorectal cancer

et al. 2021

J Exp Clin Cancer Res

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Background NOD-like receptors affect multiple stages of cancer progression in many malignancies. NACHT, LRR, and PYD domain-containing protein 7 (NLRP7) is a member of the NOD-like receptor family, although its role in tumorigenesis remains unclear. By analyzing clinical samples, we found that NLRP7 protein levels were upregulated in colorectal cancer (CRC). We proposed the hypothesis that a high level of NLRP7 in CRC may promote tumor progression. Here, we further investigated the role of NLRP7 in CRC and the underlying mechanism. Methods NLRP7 expression in human CRC and adjacent non-tumorous tissues was examined by quantitative real-time polymerase chain reaction (qRT-PCR), western blotting, and immunohistochemistry. The effect of NLRP7 in CRC progression was investigated in vitro and in vivo. Proteins interacting with NLRP7 were identified by immunoprecipitation and mass spectrometry analysis while immunofluorescence staining revealed the cellular location of the proteins. Cellular ubiquitination and protein stability assays were applied to demonstrate the ubiquitination effect on NLRP7. Cloning and mutagenesis were used to identify a lysine acceptor site that mediates NLRP7 ubiquitination. Cytokines/chemokines affected by NLRP7 were identified by RNA sequencing, qRT-PCR, and enzyme-linked immunosorbent assay. Macrophage phenotypes were determined using qRT-PCR, flow cytometry, and immunohistochemistry. Results NLRP7 protein levels, but not mRNA levels, were upregulated in CRC, and increased NLRP7 protein expression was associated with poor survival. NLRP7 promoted tumor cell proliferation and metastasis in vivo and in vitro and interacted with ubiquitin-specific protease 10, which catalyzed its deubiquitination in CRC cells. NLRP7 stability and protein levels in CRC cells were modulated by ubiquitination and deubiquitination, and NLRP7 was involved in the ubiquitin-specific protease 10 promotion of tumor progression and metastasis in CRC. K379 was an important lysine acceptor site that mediates NLRP7 ubiquitination in CRC cells. In CRC, NLRP7 promoted the polarization of pro-tumor M2-like macrophages by inducing the secretion of C-C motif chemokine ligand 2. Furthermore, NLRP7 promoted NF-κB nuclear translocation and activation of C-C motif chemokine ligand 2 transcription. Conclusions We showed that NLRP7 promotes CRC progression and revealed an as-yet-unidentified mechanism by which NLRP7 induces the polarization of pro-tumor M2-like macrophages. These results suggest that NLRP7 could serve as a biomarker and novel therapeutic target for the treatment of CRC.

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Section: Discussionmentioning

confidence: 99%

NLRP7 deubiquitination by USP10 promotes tumor progression and tumor-associated macrophage polarization in colorectal cancer

et al. 2021

J Exp Clin Cancer Res

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“…Chemokines and their receptors closely correlates with tumors, functioning critically in lymphocyte migration and tumor metastasis. 24 , 25 CXCL11 is a chemokine promoting cell proliferation and migration after binding to its receptor, and plays an extremely critical role in directional cell migration. The CXCL11 also induces inflammation and its development.…”

Section: Discussionmentioning

confidence: 99%

Elevated RBP-Jκ and CXCL11 Expression in Colon Cancer is Associated with an Unfavorable Clinical Outcome

Liu

Guo

Jiao

et al. 2021

CMAR

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“…S100 calcium binding protein A14 (S100A14) promoted cancer metastasis by upregulating the expression and secretion of CCL2 and CXCL5 via RAGE/NF-κB pathway (Fig. 2 ) 42 . These findings provided new therapeutic strategies for inhibiting breast cancer metastasis.…”

Section: Tumor Metastasismentioning

confidence: 99%

Progress of Breast Cancer basic research in China

Wang

Guan

et al. 2021

Int. J. Biol. Sci.

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Breast cancer is the most commonly diagnosed and the most lethal cancer in females both in China and worldwide. Currently, the origin of cancer stem cells, the heterogeneity of cancer cells, the mechanism of cancer metastasis and drug resistance are the most important issues that need to be addressed. Chinese investigators have recently made new discoveries in basic breast cancer researches, especially regarding cancer stem cells, cancer metabolism, and microenvironments. These efforts have led to a deeper understanding of drug resistance and metastasis and have also indicated new biomarkers and therapeutic targets. These findings emphasized the importance of the cancer stem cells for targeted therapy. In this review, we summarized the latest important findings in this field in China.

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A S100A14-CCL2/CXCL5 signaling axis drives breast cancer metastasis

Cited by 44 publications

References 45 publications

NLRP7 deubiquitination by USP10 promotes tumor progression and tumor-associated macrophage polarization in colorectal cancer

NLRP7 deubiquitination by USP10 promotes tumor progression and tumor-associated macrophage polarization in colorectal cancer

Elevated RBP-Jκ and CXCL11 Expression in Colon Cancer is Associated with an Unfavorable Clinical Outcome

Progress of Breast Cancer basic research in China

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