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Keratinocyte Growth Factor (KGF) Induces Podosome Formation via integrin-Erk1/2 Signaling in Human Immortalized Oral Epithelial Cells

Keratinocyte Growth Factor (KGF) Induces Podosome Formation via integrin-Erk1/2 Signaling in Human Immortalized Oral Epithelial Cells

Guoliang Sa, Zhikang Liu, Jiangang Ren, Qilong Wan, Xuepeng Xiong, Zili Yu, Heng Chen, Yifang Zhao, Sangang He

Cell Signal. 2019 Sep;61:39-47.

PMID: 31082464

Abstract:

Recent study established the role of integrins in keratinocyte growth factor (KGF)-induced oral epithelial adhesion and rete peg elongation. However, how extracellular matrix (ECM) remodeling cooperates with the increased epithelial adhesion during rete peg elongation has yet to be determined. Podosomes are cell-matrix contact structures that combine several abilities, including adhesion and matrix degradation. In the present study, we identified podosome formation at the ventral side of human immortalized oral epithelial cells (HIOECs) upon KGF treatment. Moreover, podosomal components including integrin α6,β4,α3,β1 and MMP14 colocalized with the F-actin-cortactin complex and matrix degradation assays demonstrated the ability of the F-actin-cortactin complex to degrade matrix. Inhibition both of integrin subunits β4 and β1 with specific blocking antibodies and inhibition of Erk1/2 abrogated the KGF-induced podosome formation. Notably, knockdown of integrin subunits β4 and β1 with specific small interfering RNA (siRNA) downregulated the phosphorylation levels of Erk1/2. In contrast, inhibition of both Erk1/2 could upregulate the expression of integrin subunits β4 and β1. These results demonstrate that KGF induces podosome formation via integrin-Erk1/2 signaling in HIOECs, suggesting a novel mechanism by which integrins enhance oral epithelial adhesion and rete peg elongation.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR42413257	KGF human			Price

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