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Atypical Growth Factor Induction of Circular Dorsal Ruffles in Hepatocellular Carcinoma Cells

By: Justine Landin, PhD
Posted: Thursday, November 17, 2022

Specific signaling molecules associated with circular dorsal ruffles that are induced by growth factors may be an effective therapeutic target for patients with some types of hepatocellular carcinoma, according to Sei Yoshida, MD, of Nankai University, Tianjin, China, and colleagues. In fact, growth factor treatment selectively increased expression of circular dorsal ruffles and activated the AKT protein kinase pathway in hepatocellular carcinoma Hep3B cell lines. The findings of this study were published in the journal Cell Communication and Signaling.

“We revealed that circular dorsal ruffles are induced in Hep3B cells as a process to arrange the growth factor-receptor—mediated phosphatidylinositol 3-kinase-AKT pathway. Based on these findings, we propose that circular dorsal ruffles in cancer cells are abnormal and trigger aberrant growth factor signaling,” stated the study investigators.

Hep3B, HepG2, BxPC-3, LO2, Huh7, and MDA-MB-231 cells were cultured and exposed to recombinant human epidermal growth factor (EGF) and insulin. The impact of EGF exposure on the expression of circular dorsal ruffles and the level of AKT and phosphorylated AKT was examined using a variety of methods, including ImageJ software, immunofluorescence staining, confocal microscopy, and scanning electron microscopy.

The formation of circular dorsal ruffles was observed only after EGF administration in the Hep3B hepatocellular carcinoma cell lines. The other five cancer cell lines did not exhibit this response, including hepatocyte and hepatocellular carcinoma cells. EGF-induced formation of circular dorsal ruffles also activated the PI3K-PIP3-AKT pathway and increased associated receptor expression. Inhibition of circular dorsal ruffles reduced the activation of the PI3K-AKT pathway in the Hep3B cell lines.

“We propose that [circular dorsal ruffles] in Hep3B would determine the carcinoma characteristic of the cell by aberrantly triggering the AKT pathway,” the study authors concluded.

Disclosure: The study authors reported no conflicts of interest.

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