CCR7 mediates human breast cancer cell invasion, migration by inducing epithelial–mesenchymal transition and suppressing apoptosis through AKT pathway

Abstract

Chemokine and the chemokine receptor have a key role in the tumor progress. Here, we supposed that CCR7 might induce the invasion, migration, and epithelial–mesenchymal transition (EMT) process of breast cancer. In this research, human breast cancer MCF‐7 and MDA‐MB‐231cells were treated with CCL19 and small‐interfering RNA (CCR7 siRNA) for activation and inhibition of CCR7, respectively. Cell invasion and transwell assays were used to detect the effect of CCR7 on invasion and migration. The results demonstrated that CCL19 mediated cell invasion and migration by inducing the EMT, with downregulation of E‐cadherin and up‐regulation of N‐cadherin and vimentin levels. On the other hand, knockdown of CCR7 revealed the changes compared with CCL19 group and the control group. Knockdown of CCR7 inhibits CCL19‐induced breast cancer cell proliferation, the cell cycle, migration, invasion and EMT. Moreover, we demonstrated that CCL19‐induced AKT phosphorylation; however, CCR7 siRNA suppressed CCL19‐induced AKT phosphorylation, a key regulator of tumor metastasis. In conclusion, all findings demonstrated that CCL19/CCR7 axis regulated EMT progress in breast cancer cells and mediated the tumor cell invasion and migration process via activation of AKT signal pathway. Our results suggested that CCR7 may regard as a therapeutic target for the breast cancer treatment.

The Role of CCL21/CCR7 Chemokine Axis in Breast Cancer Progression

“…CCL21 induces actin polymerization and migration. [18,[44][45][46] Human Bladder Cancer Enhances the migration, invasion and tumor proliferation/ correlates with poor prognosis. [43,47] Cervical Cancer Metastasis and poor prognosis.…”

“…It has been illustrated that CCR7 triggers AKT which eventually leads to the secretion of MMP-2/9. The silencing of CCR7 thus acts as a targeted therapy to inhibit AKT and MMPs expression and attenuates MCF-7 cell proliferation, invasion and EMT [45]. A schematic illustration of CCR7 binding to the cognate ligands CCL19/CCL21 to induce several signaling transduction pathways in breast cancer is shown in (Figure 2).…”

“…To provide further insight into chemokine-mediated metastatic mechanisms, the expression of CCR7 on mammary epithelial cell lines was modulated using an shRNA system based on the ability to deliver and stably express shRNAs, to study the effect of chemokine modulation on the metastatic propensity of breast cancer cells in vivo [125]. The silencing of CCR7 decreased the in vitro proliferation, migration and invasion of CCL21/CCL19-induced MCF-7 and MDA-MB-231 breast cancer cells [45,126]. Furthermore, the depletion of CCR7 in BALB/c mice inhibited orthotopically injected 4T1 cells metastasis, while tail veins' injection had no impact on breast cancer metastasis.…”

Impact of chemotactic factors and receptors on the cancer immune infiltrate: a bioinformatics study revealing homogeneity and heterogeneity among patient cohorts

“…58–60 Similar observations have been reported for the CCR2-CCL2, CCR5-CCL2,3,4,5, CCR7-CCL19,21 and CCR8-CCL18 axes. 61–69 The role of FPR1 in tumor progression remains controversial as it has been associated with tumor invasion in colorectal cancer but with tumor suppression in gastric cancer. 70,71 As far as P2RY6 is concerned, Placet et al recently suggested its role in cancer cell survival.…”

Evolutionary exploitation of PD-L1 expression in hormone receptor positive breast cancer

“…In particular we focus on tumor size and metastatic risk status of the tumor. Patient data suggests that AI therapy increases the expression of both PD-L1 and chemokine receptor CCR7 in tumors (3), both of which are associated with increased (4)(5)(6). Analysis of the therapeutic interactions suggests that there may be tradeoffs between tumor size and metastatic potential, and to this end we have developed a suite of mathematical models to investigate this interaction with the goal of eventually developing a dynamic PEPI score.…”