Panoply™ Human LPAR1 Over-expressing Stable Cell Line

Here, researchers investigated the role of lysophosphatidic acid receptor 1 (LPAR1) and its interaction with the PI3K/AKT pathway in the development of intratumoral heterogeneity (ITH) in ovarian serous cystadenocarcinoma (OSC). LPAR1 staining showed significantly higher H values in lymph node metastases and recurrent lesions compared with primary lesions within the same patient. High LPAR1 expression was associated with poor progression-free and overall survival. LPAR1-silenced cells exhibited reduced biological functions in vitro, including invasion, migration, and proliferation, as well as reduced tumor formation in vivo. These functions were significantly enhanced in LPAR1-overexpressing cells both in vitro and in vivo. p-PI3K and p-AKT levels were significantly reduced in LPAR1-knockdown cells, whereas they were significantly increased in LPAR1-overexpressing cells. These studies suggest that LPAR1 plays a crucial role in the invasion, migration, and proliferation of heterogeneous subsets of OSC cell lines, as well as in the development of ITH in OSC, potentially by regulating the activity of the PI3K/AKT pathway.

Transwell invasion/migration assays showed (Figure 1a) that the invasion and migration abilities of LPAR1 knockdown cells were significantly reduced compared with the corresponding control groups. However, the invasion/migration abilities of LPAR1 overexpressing cells were significantly enhanced compared with the corresponding control groups. A cell proliferation assay using a CCK-8 assay was performed to examine the effect of LPAR1 on cell proliferation (Figure 1b). Cell growth curves showed that LPAR1 knockdown inhibited the proliferation of A-Lv-shLPAR1 and S-Lv-shLPAR1 cells. Conversely, LPAR1 overexpression promoted the proliferation of A-Lv-LPAR1 and S-Lv-LPAR1 cells. Furthermore, there were no differences in invasion, migration, or proliferation between the control group and the corresponding wild-type group. The researchers also investigated the correlation between LPAR1 expression and the PI3K/AKT pathway. Western blot analysis revealed that p-PI3K and p-AKT levels were significantly decreased in LPAR1 knockdown cells compared with the control group, whereas they were significantly increased in LPAR1 overexpressing cells (Figure 1c).

Figure 1. Role of LPAR1 in modulating biological functions and the correlation between LPAR1 expression and the PI3K/AKT pathway. (Cui R, et al., 2019)