CCL21/CCR7 Axis Contributed to CD133+ Pancreatic Cancer Stem-Like Cell Metastasis via EMT and Erk/NF-κB Pathway

Zhang, Lirong; Wang, Dongqing; Li, Yumei; Liu, Yanfang; Xie, Xiaodong; Wu, Yingying; Zhou, Yuepeng; Ren, Jing; Zhang, Jianxin; Zhu, Haitao; Su, Zhaoliang

doi:10.1371/journal.pone.0158529

Cited by 51 publications

(42 citation statements)

References 36 publications

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“…It is known that ERK, as a mitogen-activated protein kinase signal transduction pathway, is modulated by the activity of CCR7 (28)(29)(30)(31)(32). The present study demonstrated that overexpression of CCR7 significantly increased the gene and protein expression levels of ERK.…”

Section: Discussionsupporting

confidence: 64%

CCR7 regulates ANO6 to promote migration of pancreatic ductal adenocarcinoma cells via the ERK signaling pathway

et al. 2018

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The increase in migratory ability of pancreatic ductal adenocarcinoma cells is a key event in the development of metastasis to the lymph nodes and distant organs. Although the C-C motif chemokine receptor 7 (CCR7) and its ligand, C-C motif chemokine ligand 21 (CCL21), have been revealed to serve an important role in tumor migration, their precise roles and potential underlying mechanisms remain largely unknown. The present study revealed that overexpression of CCR7 significantly promoted BxPC-3 cell migration, accompanied by the induction of anoctamin 6 (ANO6) expression, indicating that ANO6 is a downstream target of CCR7 signaling. Furthermore, the level of phosphorylated extracellular signal-regulated kinase (ERK) was significantly increased in CCR7-overexpressing BxPC-3 cells, indicating that ERK may be a potential mediator of CCR7-regulated ANO6 expression in BxPC-3 cells. To characterize the receptor-mediated pathway, a specific ERK inhibitor, U0126, was used, which reduced BxPC-3 cell migration and the expression of ANO6. In summary, the results of the present study demonstrate that CCR7 promoted BxPC-3 cell migration by regulating ANO6 expression perhaps via activation of the ERK signaling pathway.

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Section: Discussionsupporting

confidence: 64%

CCR7 regulates ANO6 to promote migration of pancreatic ductal adenocarcinoma cells via the ERK signaling pathway

et al. 2018

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“…294 C-C chemokine receptor 7 interacts with its ligand chemokine ligand 21 to inhibit apoptosis and induce survival and migration in CD133 + pancreatic cancer stem-like cells by increasing the expression of extracellular signal-regulated kinase 1/2 (Erk1/2) and p65. 295 Furthermore, B cell-specific Moloney murine leukemia virus integration site 1 (Bmi-1) also enhances the p65 protein in gastric CSCs. 296 MicroRNAs also play an important role in promoting the proliferation of CSCs.…”

Section: Major Signaling Pathways In Cscsmentioning

confidence: 99%

Targeting cancer stem cell pathways for cancer therapy

Yang

Shi

Zhao

et al. 2020

Sig Transduct Target Ther

1,318

998

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Since cancer stem cells (CSCs) were first identified in leukemia in 1994, they have been considered promising therapeutic targets for cancer therapy. These cells have self-renewal capacity and differentiation potential and contribute to multiple tumor malignancies, such as recurrence, metastasis, heterogeneity, multidrug resistance, and radiation resistance. The biological activities of CSCs are regulated by several pluripotent transcription factors, such as OCT4, Sox2, Nanog, KLF4, and MYC. In addition, many intracellular signaling pathways, such as Wnt, NF-κB (nuclear factor-κB), Notch, Hedgehog, JAK-STAT (Janus kinase/signal transducers and activators of transcription), PI3K/AKT/mTOR (phosphoinositide 3-kinase/AKT/mammalian target of rapamycin), TGF (transforming growth factor)/SMAD, and PPAR (peroxisome proliferator-activated receptor), as well as extracellular factors, such as vascular niches, hypoxia, tumor-associated macrophages, cancer-associated fibroblasts, cancer-associated mesenchymal stem cells, extracellular matrix, and exosomes, have been shown to be very important regulators of CSCs. Molecules, vaccines, antibodies, and CAR-T (chimeric antigen receptor T cell) cells have been developed to specifically target CSCs, and some of these factors are already undergoing clinical trials. This review summarizes the characterization and identification of CSCs, depicts major factors and pathways that regulate CSC development, and discusses potential targeted therapy for CSCs.Signal Transduction and Targeted Therapy (2020) 5:8; https://doi.

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“…Activation of this receptor by CCL21 leads to the acquisition of EMT markers (Eto-N-cadherin switch, MMP9 expression) and increased invasive properties. This involves Erk/NF-jB signaling (Zhang et al, 2016c).…”

Section: Ccl21mentioning

confidence: 99%

EMT and inflammation: inseparable actors of cancer progression

et al. 2017

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Tumors can be depicted as wounds that never heal, and are infiltrated by a large array of inflammatory and immune cells. Tumor‐associated chronic inflammation is a hallmark of cancer that fosters progression to a metastatic stage, as has been extensively reviewed lately. Indeed, inflammatory cells persisting in the tumor establish a cross‐talk with tumor cells that may result in a phenotype switch into tumor‐supporting cells. This has been particularly well described for macrophages and is referred to as tumor‐associated ‘M2’ polarization. Epithelial‐to‐mesenchymal transition (EMT), the embryonic program that loosens cell–cell adherence complexes and endows cells with enhanced migratory and invasive properties, can be co‐opted by cancer cells during metastatic progression. Cancer cells that have undergone EMT are more aggressive, displaying increased invasiveness, stem‐like features, and resistance to apoptosis. EMT programs can also stimulate the production of proinflammatory factors by cancer cells. Conversely, inflammation is a potent inducer of EMT in tumors. Therefore, the two phenomena may sustain each other, in an alliance for metastasis. This is the focus of this review, where the interconnections between EMT programs and cellular and molecular actors of inflammation are described. We also recapitulate data linking the EMT/inflammation axis to metastasis.

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CCL21/CCR7 Axis Contributed to CD133+ Pancreatic Cancer Stem-Like Cell Metastasis via EMT and Erk/NF-κB Pathway

Cited by 51 publications

References 36 publications

CCR7 regulates ANO6 to promote migration of pancreatic ductal adenocarcinoma cells via the ERK signaling pathway

CCR7 regulates ANO6 to promote migration of pancreatic ductal adenocarcinoma cells via the ERK signaling pathway

Targeting cancer stem cell pathways for cancer therapy

EMT and inflammation: inseparable actors of cancer progression

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