NCAPD2 stimulates glycolysis and esophageal cancer metastasis through Wnt5A-dependent Notch activation

Although non-SMC condensin I complex subunit D2 (NCAPD2) is a significant player in multiple tumors, its role in esophageal cancer (EC) remains poorly defined. This study aimed to investigate the molecular mechanisms by which NCAPD2 influenced EC metastasis.

The mechanism of NCAPD2 in EC cells was analyzed through transcriptome sequencing. The extracellular acidification rate (ECAR), oxygen consumption rate (OCR), lactate production, and glucose consumption were measured using assay kits to evaluate the level of glycolytic metabolism. Western blot was used to validate the expression of critical glycolytic enzymes, EMT markers, and Notch signaling components. Cell migration and invasion were assessed through scratch and Transwell assays. In vivo experiments included the establishment of subcutaneous tumors in BALB/c nude mice to monitor tumor growth and assess invasiveness via H&E staining. The expression of NCAPD2, Wnt5A, Notch pathway, and EMT-related proteins was detected by immunohistochemistry.

NCAPD2 overexpression in EC cells enhanced their ability to migrate and invade by promoting glycolysis-a process tightly linked to the activation of Wnt5A. Specifically, NCAPD2 drove up Wnt5A levels, which in turn boosted glycolytic flux. This metabolic shift relied on the activation of the Notch pathway by Wnt5A, ultimately fueling the metastatic potential of EC.

NCAPD2 enhanced the proliferation and metastasis of EC cells by promoting glycolysis through Wnt5A-mediated activation of the Notch pathway. This finding not only revealed the critical role of the NCAPD2/Wnt5A axis in EC but also provided a potential therapeutic target for EC treatment.