Placenta-specific protein 1 enhances liver metastatic potential and is associated with the PI3K/AKT/NF-κB signaling pathway in colorectal cancer

Colorectal Cancer
23/07/2020

Eur J Cancer Prev. 2020 Jul 21. doi: 10.1097/CEJ.0000000000000611. Online ahead of print.

ABSTRACT

To better explore the underlying mechanism of liver metastatic formation by placenta-specific protein 1 (PLAC1) in human colorectal cancer, we investigated the proliferation, invasion and angiogenic capabilities of human colorectal cancer cells with different liver metastatic potentials as well as the mechanism of action of PLAC1 in the metastatic process. The expression of PLAC1 was detected by reverse transcriptase PCR, western blot, and real-time PCR. The effect of PLAC1 on metastatic


potential was determined by proliferation, invasion, and angiogenesis assays, including an in-vitro coculture system consisting of cancer cells and vascular endothelial cells that were used to detect the relationship between cancer cells and angiogenesis. In addition, we also determined PLAC1 downstream targets that preferentially contribute to the metastatic process. PLAC1 was expressed in HT-29, WiDr, and CaCo-2 colorectal cancer cells but not in Colo320 colorectal cancer cells. PLAC1 not only enhanced significantly the proliferation of CoLo320 and human umbilical vein endothelial cells (HUVECs) but also promoted the invasion of CoLo320 cells. The angiogenesis of HUVECs was enhanced by PLAC1 in a dose-dependent manner. In cocultured systems, angiogenesis was significantly increased by coculture with HT-29 cells. In addition, PLAC1 could promote angiogenesis in coculture with HT-29 cells. Furthermore, PLAC1-enhanced metastatic potential of colorectal cancer cells was dependent on the activation of the PI3K/Akt/NF-κB pathway. The activation of PI3K/Akt/NF-κB signaling by PLAC1 may be critical for metastasis of colorectal cancer cells. According to our results, we suggest that modification of PLAC1 function might be a promising new therapeutic approach to inhibit the aggressive spread of colorectal cancer.