The Role of PROX1 in Neoplasia: A Key Player Often Overlooked

Abstract

The human PROX1 gene (Prospero homeobox gene 1) is a member of the homeobox transcription factor family. PROX1 plays a key role in the development of the lymphatic system and is primarily used as a lymphatic vessel marker. However, as the accumulating evidence indicates that PROX1 is also implicated in the tumorigenesis of various cancer types, the scientific community has attempted to elucidate its complicated function in neoplasia pathogenesis, as well as its utility in cancer diagnosis, prognosis, and therapy. PROX1 has been shown to participate in the complex molecular mechanisms affecting tumorigenesis and has been associated with a plethora of clinicopathological parameters, including tumor stage and patients’ overall survival. Depending on the specific organ affected, PROX1 has exhibited both tumor-promoting and tumor-suppressing properties, with its inhibition and reactivation representing possible novel therapeutic interventions, respectively. Moreover, researchers have reported PROX1 as a useful tool in the fields of diagnosis and prognosis assessment. The current study aims to summarize and present the existing data that render PROX1 a novel and useful diagnostic and prognostic biomarker, as well as a possible therapeutic target.

Upregulation of Cell Surface Glycoproteins in Correlation with KSHV LANA in the Kaposi Sarcoma Tumor Microenvironment

“…Despite variable transcriptomic expression (on average 1.40-fold upregulated), CD34 was included for lineage discrimination since it has been detected previously in KS lesions at the protein level and is a marker for vascular endothelial cells and hematopoietic stem cells [ 18 , 23 ]. Prox-1, a nuclear marker for lymphatic endothelial cells, was included for lineage discrimination; it was upregulated 21.52-fold in KS tumors and highly correlated with KSHV LANA [ 16 ]. Prox-1 has also been implicated in KSHV maintenance in cell culture models and may also contribute to lytic reactivation [ 15 ].…”

“…The upregulation of FLT4 has also been observed in some KSHV-infected endothelial cell lines [ 14 ]. In vitro findings from KSHV-infected primary endothelial cells linked the expression of FLT4 with an increased expression of the transcription factor Prox-1, a lineage-defining marker of lymphatic endothelial cells [ 15 , 16 ]. An alternate endothelial cell marker CD34, also found on hematopoietic stem cells, is known to be robustly expressed in KS lesions, [ 17 , 18 ].…”