CCR9 in cancer: oncogenic role and therapeutic targeting

Adult T-cell acute lymphoblastic leukemia (T-ALL) is a refractory leukemia. We previously showed that CCL25/CCR9 promotes T-ALL metastasis. In the present study, we assessed the effects of CCL25 on Wnt expression and the effects of Wnt5a and CCL25 on PI3K/Akt and RhoA activation. Transwell assays and mouse xenograft experiments were utilized to assess the effects of Wnt5a and CCL25 on MOLT4 cell invasion, migration and metastasis. The effects of Wnt5a on MOLT4 cell actin polarization and pseudopodium formation were examined using laser scanning confocal microscopy and scanning electron microscopy. CCL25 induced Wnt5a expression in MOLT4 cells by promoting protein kinase C (PKC) expression and activation. Wnt5a promoted MOLT4 cell migration, invasion, actin polarization, and lamellipodium and filopodia formation via PI3K/Akt-RhoA pathway activation. These effects were rescued by PI3K/Akt or RhoA knockdown or inhibition. Additionally, Wnt5a in cooperation with CCL25 promoted MOLT4 cell mouse liver metastasis and stimulated RhoA activation. These results show that CCL25/CCR9 upregulates Wnt5a by promoting PKC expression and activation in MOLT4 cells. This in turn promotes cell migration and invasion via PI3K/Akt-RhoA signaling, enhancing cell polarization and pseudopodium formation. These findings indicate that the PI3K/Akt-RhoA pathway is likely responsible for Wnt5a-induced adult T-ALL cell migration and invasion.

show abstract

“…CCR9 expression is selectively increased on CD4 + T cells in T-ALL, inducing chemotactic migration by T-ALL CD4 + cells [20, 21]. …”

Section: Introductionmentioning

confidence: 99%

Wnt5a and CCL25 promote adult T-cell acute lymphoblastic leukemia cell migration, invasion and metastasis

Deng

Xiong

et al. 2017

Oncotarget

Self Cite

View full text Add to dashboard Cite

show abstract

“…Chemokines/chemokine receptors take part in all stages of tumor development, including immune cells recruitment, neovascularization, tumor proliferation, invasion, and metastasis [26,27]. CCR9 interacts with its exclusive ligand CCL25 and results in trafficking of both lymphocytes and tumor cells to participate in tumor immunity and tumor development [11,16,17,[27][28][29][30]. More and more studies have indicated that CCR9 could be viewed as an oncogenic biomarker in predicting metastasis and prognosis for cancer patients.…”

Section: Discussionmentioning

confidence: 99%

“…Increased CCR9 expression was correlated with poor overall survival [9,14]. CCR9/CCL25 axis played an important role in tumor invasion, migration, drug resistance and apoptosis [15,16]. The application of anti-CCR9 antibody could inhibit the migration and invasion of tumor cells [17].…”

Section: Introductionmentioning

confidence: 99%

CCR9 Promotes Migration and Invasion of Lung Adenocarcinoma Cancer Stem Cells

Lü¹,

Du²,

Huang³

et al. 2020

Int. J. Med. Sci.

View full text Add to dashboard Cite

Aim: CC chemokine receptor 9 (CCR9) interacts with its exclusive ligand CCL25, resulting in promoting tumor progression and metastasis. However, the effect and mechanisms of CCR9 on lung adenocarcinoma distant metastasis remain largely unknown. To preliminary clarify the underlying mechanisms, we investigate the correlation between CCR9 and ALDH1A1 + cancer stem cells (CSCs), as well as the effect of CCR9 on the migration and invasion of CSCs. Methods: Immunohistochemistry was performed to detect the expression of CCR9 in lung adenocarcinoma tissues. The correlations of CCR9 with distant metastasis and overall survival were investigated. Serial paraffin-embedded tissue blocks were used to detect ALDH1A1 + CSCs expression. The correlations between CCR9 expression and ALDH1A1 + CSCs were evaluated. We further studied the effect of CCR9/CCL25 on the migration and invasion of CSCs using transwell assays. Results: There were positive correlations between CCR9 expression and distant metastasis, as well as poor overall survival. Patients with high CCR9 expression were more likely to develop distant metastasis and demonstrated poorer overall survival than patients with low CCR9 expression. In addition, there was positive correlation between the expression of CCR9 and ALDH1A1 in the same tumor microenvironment. ALDH high CSCs demonstrated enhanced expression of CCR9 than ALDH low cells. Further transwell assays demonstrated that the numbers of CSCs migrated or invaded in response to CCL25 were more than that without CCL25 stimulation. Additional application of anti-CCR9 antibody reversed the CCL25-induced migration and invasion of CSCs. Conclusions:In summary, our study demonstrated that CCR9/CCL25 promoted the migration and invasion of CSCs, which might contribute to distant metastasis and poor overall survival. Our findings provided evidence that CCR9/CCL25 could be used as novel therapeutic targets for lung adenocarcinoma.

show abstract

“…These results indicate that piscine CCR9 were predominantly expressed in hematopoietic and/or immune-related tissues, such as the blood, head kidney, kidney, and gill. In mammals, CCR9 was mainly distributed in immature T lymphocytes and on the surface of intestinal cells (Tu et al 2016). Recent studies have provided Figure 4.…”

Section: Tissue Distribution Of the Rcccr9mentioning

confidence: 99%

Molecular characterization and expression analysis of the CCR9 gene from cobia (Rachycentron canadum) following bacterial and poly I:C challenge

Deng

Cheng

et al. 2019

Journal of Applied Animal Research

View full text Add to dashboard Cite

Chemokine receptors play an important role in coordination of cell trafficking in many biological processes. In this study, a CC chemokine receptor 9 of cobia Rachycentron canadum (RcCCR9) was identified. Analysis of the ORF (1119 bp) of RcCCR9 revealed a predicted protein of 41.87 kDa with typical seven transmembrane domain architecture. RcCCR9 shared several conserved structural features with homologs from mammals and other fish, and had a consistent relationship with phylogenetic trees and sequence identities. Reverse transcription quantitative PCR analysis showed ubiquitous RcCCR9 transcripts in healthy cobia, mainly in immune-related organs, with the highest levels in blood and lower levels in intestines and brain. After challenge with inactivated Vibrio harveyi or viral mimic poly I:C, RcCCR9 expression was up-regulated in head kidney and down-regulated in spleen. Compared with poly I:C, V. harveyi induced a stronger up/down-regulation of CCR9 mRNA levels in the central immune organs. RcCCR9 seems to be strongly involved in host defense against bacterial infection. ARTICLE HISTORY

show abstract

CCR9 in cancer: oncogenic role and therapeutic targeting

Cited by 67 publications

References 65 publications

Wnt5a and CCL25 promote adult T-cell acute lymphoblastic leukemia cell migration, invasion and metastasis

Wnt5a and CCL25 promote adult T-cell acute lymphoblastic leukemia cell migration, invasion and metastasis

CCR9 Promotes Migration and Invasion of Lung Adenocarcinoma Cancer Stem Cells

Molecular characterization and expression analysis of the CCR9 gene from cobia (Rachycentron canadum) following bacterial and poly I:C challenge

Contact Info

Product

Resources

About