Panoply™ Human GRIN2B Knockdown Stable Cell Line

Endometrial cancer (EC) remains a lethal gynecological malignancy, with limited therapeutic options due to its poorly understood pathogenesis. Cellular senescence is a key barrier to cancer cell tumorigenesis, making investigation of its role in EC progression a critical research avenue to address these challenges. Here, researchers revealed a critical role for cellular senescence in EC progression through multi-omics analysis and functional validation. Integrative analysis of RNA sequencing and clinical datasets revealed that Na+/H+ exchanger 7 (NHE7), a prognostic biomarker, is significantly overexpressed in EC tissue. Functional studies revealed that NHE7 overexpression promotes cell proliferation, motility, and cell cycle progression, while inhibiting senescence-associated markers and cytokine secretion. Conversely, knockdown of NHE7 reversed these oncogenic phenotypes. Mechanistically, NHE7 binds to the cAMP-related transcription factor, thereby increasing GRIN2B expression, which in turn enhances intracellular Ca²⁺ influx, delaying cellular senescence and promoting cancer progression in vitro and in vivo. These findings suggest that NHE7 plays a crucial role in delaying cellular senescence and promoting endometrial cancer (EC) progression through the cAMP pathway, revealing a key driver of EC pathogenesis and indicating a viable therapeutic target.

Here, the researchers constructed GRIN2B knockdown Ishikawa cells and confirmed its knockdown efficiency by Western blotting (WB) experiments (Figure 1A). Similarly, the data showed that GRIN2B knockdown partially reversed NHE7-induced EC cell senescence resistance, as reflected in calcium levels, β-galactosidase activity, and cell cycle distribution (Figure 1B-D). This also inhibited proliferation, altered the expression of senescence-related molecules, and reduced the expression of SASP-related molecules, which was caused by NHE7-induced senescence resistance (Figure 1E-F). In summary, GRIN2B knockdown effectively reversed NHE7-induced EC cell senescence resistance, highlighting the key role of GRIN2B in NHE7-regulated EC senescence.

Figure 1. Knocking down GRIN2B reverses NHE7-mediated senescence resistance of EC cells. (Yang S, et al., 2025)