Oncogenic function of Plac1 on the proliferation and metastasis in hepatocellular carcinoma cells

Abstract

Placenta-specific protein 1 (Plac1), which is selectively expressed in the placental syncytiotrophoblast in adult normal tissues, plays an essential role in normal placental and embryonic development. Accumulating evidence suggests that enhanced Plac1 expression is closely associated with the progression of human cancer. Whether Plac1 contributes to the pathophysiology of hepatocellular carcinoma (HCC) remains unclear. In the present study, our data revealed that the expression of Plac1 in human HCC tissues was upregulated, which significantly correlated with metastasis of HCC. Knockdown of Plac1 by small interfering RNA (siRNA) in Bel-7402 and HepG2 cells resulted in decreasing tumor cell proliferation and increasing apoptosis, which implied the oncogenic potential of Plac1. Moreover, silencing of Plac1 induced G1 cell cycle arrest through suppression of cyclin D1 and CDK4 expression. Furthermore, depletion of Plac1 repressed epithelial-mesenchymal transition (EMT), with decreased cell migration and invasion, supporting upregulated E-cadherin expression and downregulated vimentin, twist and snail expression that characterize EMT. Further study suggested that decreased Plac1 expression attenuated the phosphorylation of Akt. These findings have uncovered that Plac1 plays a pivotal role in the progression of HCC, and may serve as a novel therapeutic target for HCC.

Placenta‐specific 1 regulates oocyte meiosis and fertilization through furin

“…Akt dysfunction could be another cause of low fertilization in Plac1-reduced oocytes. In cultured cancer cells, Plac1 did regulate Akt phosphorylation (25).…”

Cancer/testis antigen‐Plac1 promotes invasion and metastasis of breast cancer through Furin/NICD/PTEN signaling pathway

“…Placenta-specific protein 1 (Plac1), a known CTA, is primarily expressed in cytomembrane of the trophoblastic lineage, and plays an important role in the development of human placenta, including trophoblast invasion and migration (Chang et al, 2014). While its expression is mostly restricted to placenta and testis in normal tissues, Plac1 is frequently activated and highly expressed in wide variety of human cancers (Devor and Leslie, 2013;Ghods et al, 2014;Liu et al, 2015;Silva et al, 2007;Wu et al, 2017). Moreover, Plac1 possesses cancer-specific immunogenicity that makes it a potential target for cancer immunotherapy (Liu et al, 2012).…”

“…Moreover, Plac1 possesses cancer-specific immunogenicity that makes it a potential target for cancer immunotherapy (Liu et al, 2012). Emerging evidence has indicated that Plac1 is involved in regulation of tumor metastasis and progression (Koslowski et al, 2007;Nagpal et al, 2013;Wu et al, 2017). For example, a previous study using siRNA inhibition of Plac1 in breast cancer cell lines effectively suppressed tumor migration and invasion (Koslowski et al, 2007).…”

Placenta-Specific Protein 1 Enhances Liver Metastatic Potential and is Associated with the PI3K/AKT/NF-κB Signaling Pathway in Colorectal Cancer

“…The results showed that exogenous PLAC1 could significantly increase the proliferation and invasion of the PLAC1-negative colorectal cancer cell line Yuan H et al [27] showed that PLAC1 was expressed in up to 37.8% of primary tumor specimens, especially in 82.3% and 54.6% of primary breast cancer and tumor cell lines, respectively. Silencing of the PLAC1 gene and anti-PLAC1 antibody can significantly inhibit the motility, proliferation and invasiveness of non-small cell lung cancer [28]. Moreover, silencing PLAC1 by siRNA and blocking PLAC1 by anti-PLAC1 antibody led to a decrease in phosphorylated Akt levels [29].…”