ISSN: 1837-9664Journal of Cancer
Global reach, higher impact
J Cancer 2024; 15(10):2981-2993. doi:10.7150/jca.89970 This issue Cite
Research Paper
Decreased Expression of PLD2 Promotes EMT in Colorectal Cancer Invasion and Metastasis
1. Department of General Surgery, Central Hospital of Xuhui District, Shanghai, China.
2. Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
† These authors have contributed equally to this work and share first authorship.
Abstract
Background and Objectives: PLD2 has been identified as playing a critical role in cancer cell motility and migration and other pathophysiological processes. We investigated the expression of PLD2 and its biological functions and clinical implications in human colorectal cancer.
Materials and Methods: In this study, the expressions of PLD2 were analyzed in CRC cell lines and CRC samples by RT-PCR, western blot and immunohistochemistry. The PLD enzyme activity was studied using an PLD detection kit. We also performed matrigel invasion assay to evaluate the invasive capabilities in CRC cells. The expressions of EMT-related markers were quantified at mRNA and protein level using RT-PCR and western blot. We performed high-throughput RNA sequencing on PLD2 knockdown and overexpression CRC cell lines to explore the changes in gene expression associated with PLD2.
Result: Herein, we showed that PLD2 expression was relatively low in CRC cell lines and CRC samples and PLD2 deficiency was significantly correlated with more advanced clinical phenotype regarding lymphatic and distant metastasis and poor patient survival. We also detected that PLD2 knockdown favored epithelial-mesenchymal transition (EMT) and thus promoted CRC invasion and metastasis. Further exploration uncovered that the expressions of several important genes closely related to metabolic pathways in CRC were noticeably altered due to PLD2 deficiency, including ID1, IFIT4, OASL, IFIT2 and CTAG2.
Conclusion: Our results revealed that PLD2 deficiency promotes cell invasion and metastasis in CRC via EMT indicating PLD2 might have an important implication in carcinogenesis and progression and would be a new therapeutic target for cancer treatment.
Keywords: PLD2, invasion, metastasis, EMT, colorectal cancer
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