HAb18G/CD147 promotes cell motility by regulating annexin II-activated RhoA and Rac1 signaling pathways in hepatocellular carcinoma cells

Abstract

Tumor cells can move as individual cells in two interconvertible modes: mesenchymal mode and amoeboid mode. Cytoskeleton rearrangement plays an important role in the interconversion. Previously, we reported that HAb18G/CD147 and annexin II are interacting proteins involved in cytoskeleton rearrangement, yet the role of their interaction is unclear. In this study we found that the depletion of HAb18G/CD147 produced a rounded morphology, which is associated with amoeboid movement, whereas the depletion of annexin II resulted in an elongated morphology, which is associated with mesenchymal movement. The extracellular portion of HAb18G/CD147 can interact with a phosphorylation-inactive mutant of annexin II and inhibit its phosphorylation. HAb18G/CD147 inhibits Rho signaling pathways and amoeboid movement by inhibiting annexin II phosphorylation, promotes membrane localization of WAVE2 and Rac1 activation by way of the integrin-FAK-PI3K/PIP3 signaling pathway, and promotes the formation of lamellipodia and mesenchymal movement. Conclusion: These results suggest that the interaction of HAb18G/CD147 with annexin II is involved in the interconversion between mesenchymal and amoeboid movement of hepatocellular carcinoma cells.

GPR116, an Adhesion G-Protein–Coupled Receptor, Promotes Breast Cancer Metastasis via the Gαq-p63RhoGEF-Rho GTPase Pathway

“…We further showed that RhoA and Rac1 were responsible for GPR116-induced cancer cell migration and morphology changes. Previous studies have shown that RhoA and Rac1 regulate the formation of an elongated cell morphology in macrophages (37) and regulate the motility of diverse tumor cells (38)(39)(40), which are consistent with our observations. Second, we found that GPR116 promoted breast cancer cell migration and invasion via Gaq signaling.…”

Extracellular Membrane-proximal Domain of HAb18G/CD147 Binds to Metal Ion-dependent Adhesion Site (MIDAS) Motif of Integrin β1 to Modulate Malignant Properties of Hepatoma Cells

“…As a transmembrane glycoprotein, CD147 localizes to both the cell membrane and the endomembrane system in HCC cells. A recent study in our laboratory has proved that CD147 localizing to endomembrane system inhibits the RhoA/ ROCK signaling pathway and amoeboid movement via depression of annexin II phosphorylation (24). Although a previous study claimed that the ERK pathway was involved in FAK regulation by CD147 (23), further investigation is needed to study the responsible mechanism.…”

CD147, CD44, and the Epidermal Growth Factor Receptor (EGFR) Signaling Pathway Cooperate to Regulate Breast Epithelial Cell Invasiveness

“…We and others have demonstrated that CD147 influences migration and invasion via protease induction and cytoskeletal remodeling (10,27,66,67), although the exact signaling mechanisms regulating these processes are not understood. Here we have shown that up-regulation of CD147 in non-transformed breast epithelial cells leads to increased EGFR, Ras, and ERK activation.…”