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Differential expression of Axl in hepatocellular carcinoma and correlation with tumor lymphatic metastasis
Ling He1, Jianing Zhang, Lili Jiang
1College of Laboratory Medicine, Dalian Medical University, Liaoning Province, China.
Abstract:
Protein kinases play important roles in tumor development and progression. A variety of members of the signal transduction enzymes serve as targets for therapeutic intervention in cancer. The dysregulation of Axl receptor and its ligand growth arrest-specific 6 (Gas6) is implicated in the pathogenesis of several cancers. In this study, the differential expressions of Axl were investigated in mouse hepatocarcinoma cell lines Hca-F and Hca-P, which have high- and low-metastatic potential to lymph nodes. Experimental inhibition of Axl by siRNA assessed further the metastatic potential of Axl. The results showed that down-regulation of Axl expression attenuated Hca-F cells proliferation, migration, and invasion in vitro, as well as inhibited metastasis to peripheral lymph nodes in vivo. Further analysis demonstrated that the addition of exogenous Gas6 mediated the migration and invasion of Hca-F cells both in vitro and in vivo through Axl. Furthermore, Gas6 stimulation of Axl in Hca-F cells resulted primarily in the down-regulation of Cyr61, a member of the CCN protein family involved in tumor progression. These data suggest that Axl acts as a tumor lymphatic metastasis-associated gene, and may function partly through the regulation of Cyr61.
Insights
The Axl receptor kinase promotes cancer metastasis. Inhibiting Axl reduced tumor cell growth and spread, suggesting Axl is a key target for treating metastatic cancers.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Protein kinases are crucial in cancer development and progression.
- Axl receptor and its ligand growth arrest-specific 6 (Gas6) dysregulation is linked to cancer pathogenesis.
- Targeting signal transduction enzymes offers therapeutic strategies for cancer intervention.
Purpose of the Study:
- To investigate differential Axl expression in mouse hepatocarcinoma cell lines with varying metastatic potentials.
- To assess the role of Axl in tumor cell proliferation, migration, invasion, and metastasis.
- To elucidate the mechanism by which Gas6 influences Axl-mediated cancer progression.
Main Methods:
- Differential expression analysis of Axl in Hca-F (high metastasis) and Hca-P (low metastasis) cell lines.
- Experimental inhibition of Axl using small interfering RNA (siRNA).
- In vitro assays for cell proliferation, migration, and invasion; in vivo studies for lymph node metastasis.
- Assessment of Cyr61 expression following Gas6 stimulation of Axl.
Main Results:
- Down-regulation of Axl expression reduced Hca-F cell proliferation, migration, and invasion in vitro.
- Axl inhibition significantly inhibited metastasis to peripheral lymph nodes in vivo.
- Exogenous Gas6 promoted Hca-F cell migration and invasion via Axl activation.
- Gas6 stimulation of Axl led to Cyr61 down-regulation in Hca-F cells.
Conclusions:
- Axl receptor functions as a tumor lymphatic metastasis-associated gene.
- Axl signaling pathway plays a critical role in hepatocarcinoma metastasis.
- Axl may partly regulate tumor progression through modulation of Cyr61 expression.
