Prominin-2 Prevents the Formation of Caveolae in Normal and Ovarian Hyperstimulated Pregnancy

Abstract

During early pregnancy, uterine epithelial cells (UECs) become less adherent to the underlying basal lamina and are subsequently removed so the blastocyst can invade the underlying stroma. This process involves the removal of focal adhesions from the basal plasma membrane of UECs. These focal adhesions are thought to be internalized by caveolae, which significantly increase in abundance at the time of blastocyst implantation. A recent in vitro study indicated that prominin-2 prevents the formation of caveolae by sequestering membrane cholesterol. The present study examines whether prominin-2 affects the formation of caveolae and loss of focal adhesions in UECs during normal and ovarian hyperstimulation (OH) pregnancy in the rat. At the time of fertilization during normal pregnancy, prominin-2 is distributed throughout the basolateral plasma membrane. However, at the time of implantation and coincident with an increase in caveolae, prominin-2 is lost from the basal plasma membrane. In contrast, prominin-2 remains in the basolateral plasma membrane throughout OH pregnancy. Transmission electron microscopy showed that this membrane contained few caveolae throughout OH pregnancy. Our results indicate that prominin-2 prevents the formation of caveolae. We suggest the retention of prominin-2 in the basal plasma membrane during OH pregnancy prevents the formation of caveolae and is responsible for the retention of focal adhesions in this membrane, thereby contributing to the reduced implantation rate observed after such treatments.

PROM2 overexpression induces metastatic potential through epithelial‐to‐mesenchymal transition and ferroptosis resistance in human cancers

“…We also showed in our models that CAV1 mRNA expression increased with PROM2 expression. Since CAV1 mRNA and protein overexpression can induce EMT marker overexpression in various cancer cell lines, 37–41 CAV1, that participates to caveolar endocytosis, 7,8 could be intermediate between PROM2 and EMT markers in our in vitro and in vivo melanoma models.…”

“…PROM2 expression gradually increased in the cell lines and in corresponding metastases from round 0 to round 3 (Figure 5E). Since PROM2 induces caveolin-1 (CAV1) expression and phosphorylation, 7,8 which can itself increase mRNA expression of SLUG, TWIST and VIM, [32][33][34] we assessed the expression of all these markers across successive rounds in cell lines and derived metastases. Alongside increased PROM2 expression, we showed a gradual but significant increase in mRNA expression of CAV1 and EMT markers from rounds 0 to 3 (Figure 5E).…”

“…However, its expression is higher in cilia, microvilli and other acetylated tubulin‐positive protruding structures 6 . In addition, PROM2 is involved in the regulation of caveolar endocytosis, and its overexpression leads to significant changes in plasma membrane organisation and function, including an increase of protrusions, and thus of invasive potential 7,8 …”

“…6 In addition, PROM2 is involved in the regulation of caveolar endocytosis, and its overexpression leads to significant changes in plasma membrane organisation and function, including an increase of protrusions, and thus of invasive potential. 7,8 Physiologically, PROM2 has recently been described as a ferroptosis inhibitor. 9 Ferroptosis is a form of regulated cell death characterised by iron-dependent lipid peroxidation.…”