Placenta-specific protein 1 (PLAC1) is a unique onco-fetal-placental protein and an underappreciated therapeutic target in cancer

Abstract

Placenta-specific protein 1 (PLAC1) is an X-linked gene whose expression is almost exclusively limited to placental trophoblasts. Its expression profile and evolutionary history suggest that it is important in the proper establishment and maintenance of a healthy placenta and a successful gestation throughout the Eutheria through promoting invasiveness, migration and proliferation of placental tissue. For the same reasons, PLAC1 expression has been found to be co-opted in a variety of cancers. For reasons less understood, it is also expressed in developing embryos. Thus, PLAC1 is the only known member of a class of proteins termed "onco-fetal-placental."

Placenta-Specific Protein 1 Expression in Human Papillomavirus 16/18–Positive Cervical Cancers Is Associated With Tumor Histology

“…20 Moreover, several studies of PLAC1 in human cancers have noted an association between higher relative PLAC1 expression and a poor prognosis. 3 The data presented here are consistent with those observations.…”

“…19 Since that time, induction of PLAC1 expression has been demonstrated in a wide range of cancers including hepatocellular, colorectal, gastric, breast, prostate, ovarian, and uterine tumors. 3 Here, we report for the first time that PLAC1 is also expressed in HPV-positive cervical cancers encompassing 4 histologic types.…”

“…2 Beginning only a few years after its discovery, reports began to appear indicating that PLAC1 expression is induced in a variety of human cancers. 3 It was also shown that most of PLAC1 transcripts in cancer originate from a different promoter than do transcripts in placental tissues. 4,5 In the placenta, PLAC1 is primarily transcribed from a promoter called P2 or ''proximal,'' and in tumors, PLAC1 is primarily transcribed from a promoter called P1 or ''distal.''…”

Placenta-specific1 (PLAC1) is a potential target for antibody-drug conjugate-based prostate cancer immunotherapy

“…Although most of the studies on PLAC1 expression have been oriented at the transcript level due to the uncertainty of available antibodies, the cumulative data indicate the differential overexpression of this marker in vast majority of solid tumors and cell lines 10 , 20 , 26 – 30 making anti-PLAC1 antibodies a potentially suitable vehicle for delivering cytotoxic agents to cancer cells. In spite of the wide expression pattern of PLAC1 in variety of cancers, prostate cancer seems to be the prototype model for investigation of potential therapeutic effects of anti-PLAC1-based nanomedicine due to its high prevalence 1 , 31 , 32 and differential expression of PLAC1 in PCa 8 , 33 .…”

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

“…The protein is closely related to the growth of the placenta and embryo and plays an important role in regulating the formation of the placenta and stabilizing the connection between the placenta and the mother, thus acting as a biological indicator to predict the prognosis of pathological pregnancy and embryo transfer. PLAC1 is extensively expressed in tumor tissue [23]. CT antigen is overexpressed in various tumor types, while its expression is restricted to germ cells for normal tissues.…”