Human MERTK Stable Cell Line - THP-1

MERTK is a member of the TAM (TYRO3, AXL, and MERTK) receptor tyrosine kinases that play complex and diverse roles in cell biology. To better understand the interplay between cellular transformation and exocytosis, researchers stably expressed MERTK in human MCF10A cells, a non-tumorigenic mammary epithelial cell line that lacks endogenous MERTK. While stable expression of MERTK in MCF10A enhanced motility and AKT-mediated chemoprotection, MERTK-10A cells did not form stable colonies in soft agar and did not have enhanced proliferation compared to parental MCF10A cells. In addition to conferring chemoresistance, MERTK stimulates exocytosis, resulting in gain of function. However, unlike AXL, activation of MERTK was highly dependent on apoptotic cells, suggesting that MERTK may preferentially interact with phosphatidylserine. Consistent with this idea, knockdown of MERTK in breast cancer cells MDA-MB 231 reduced exocytosis, whereas transient or stable expression of MERTK stimulated apoptotic cell clearance in all cell lines tested. Finally, apoptotic cells induced PD-L1 expression, an immune checkpoint blockade, via MERTK, suggesting that cancer cells may adopt MERTK-driven exocytosis as an immunosuppressive mechanism to their advantage.

MCF10A-MERTK cells were measured to have increased motility on a serum gradient relative to control MCF10-pMSCV cells, and addition of GAS6 to the chemotactic gradient enhanced this motility (Figure 1A). Furthermore, MERTK protected MCF10A from cell death induced by camptothecin and 5-fluorouracil (5-FU) (Figure 1B and C). As chemoresistance has been associated with altered AKT signaling, the researchers investigated AKT activation downstream of MERTK signaling. When MERTK was activated by its canonical ligand, GAS6, AKT phosphorylation was significantly elevated (Figure 1D), while ERK1/2 phosphorylation was slightly increased. To confirm that AKT mediates chemoresistance in MCF10A-MERTK cells, the PI3K/AKT inhibitor LY-294002 was used, and it was found that the chemoprotective effect of MERTK on MCF10A was indeed reversible (Figure 1B and C). Taken together, these data suggest that overexpression of MERTK in mammary epithelial cells may be beneficial to cancer cells because it can enhance cell motility and promote chemoresistance through AKT.

Figure 1. MERTK promotes migration and chemoprotection. (Nguyen K Q N, et al., 2014)

Creative Biogene has successfully constructed MERTK over-expressing stable cell lines with THP-1, MCF10A, CHO-K1, HEK293, BaF3, TE-1, CHO, HeLa, 1321N1, U2OS, etc. These MERTK stable cell lines have excellent in vitro assay sensitivity and reproducibility. Therefore, conducting experiments with our MERTK stable cell lines saves time and resources while providing more accurate results.