Paxillin knockdown suppresses metastasis and epithelial‑mesenchymal transition in colorectal cancer via the ERK signalling pathway.

Long Wen, Xiaoqian Zhang, Junling Zhang, Shanwen Chen, Yongchen Ma, Jianwen Hu, Taohua Yue, Jingui Wang, Jing Zhu, Tao Wu, Xin Wang

Oncology reports 2020 Sep

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Paxillin (PXN) is a cytoplasmic protein that plays an important role in regulating focal adhesion, cytoskeletal rearrangements and cell motility. The present study aimed to investigate the role of PXN in the metastasis of human colorectal cancer (CRC) and its possible mechanisms. Immunohistochemical staining of tissues from 102 surgical CRC patients revealed that high PXN expression was positively correlated with tumour‑node‑metastasis (TNM) stage, lymph node metastasis, distant metastasis, and recurrence at distant sites after radical surgery. In 24 cases of stage IV CRC, PXN expression in liver metastasis was higher than that in the matched primary tumour. The knockdown of PXN inhibited the proliferation, migration and invasion potential of SW480 cells in vitro and in vivo. Transmission electron microscopy revealed the effect of PXN on ultrastructural characteristics, observed mainly in microvilli and desmosomes. The downregulation of PXN decreased the activation of extracellular regulated protein kinase (ERK) and suppressed the epithelial‑mesenchymal transition (EMT) process. Following the downregulation of PXN, the addition of an ERK activator or inhibitor restored or further suppressed EMT, respectively, accompanied by corresponding changes in cell migration and invasion. Collectively, the present results confirmed the important role of PXN in CRC metastasis and revealed that PXN regulated EMT progression via the ERK signalling pathway. PXN may represent a future therapeutic strategy to prevent the EMT‑associated progression and invasion of CRC.

Citation

Long Wen, Xiaoqian Zhang, Junling Zhang, Shanwen Chen, Yongchen Ma, Jianwen Hu, Taohua Yue, Jingui Wang, Jing Zhu, Tao Wu, Xin Wang. Paxillin knockdown suppresses metastasis and epithelial‑mesenchymal transition in colorectal cancer via the ERK signalling pathway. Oncology reports. 2020 Sep;44(3):1105-1115