The receptor tyrosine kinase Axl is an essential regulator of prostate cancer proliferation and tumor growth and represents a new therapeutic target.
The receptor tyrosine kinase Axl is an essential regulator of prostate cancer proliferation and tumor growth and represents a new therapeutic target.
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受体酪氨酸激酶 Axl 的失调与多种人类癌症的进展有关。然而，Axl 在前列腺癌中的作用仍然知之甚少，Axl 靶向的治疗功效也尚未经过测试。在本报告中，我们将 Axl 确定为前列腺癌的新治疗靶点。 Axl 在前列腺癌细胞系和人类前列腺肿瘤中持续过度表达。有趣的是，Axl 基因表达的阻断强烈抑制增殖、迁移、侵袭和肿瘤生长。此外，小干扰 RNA 对 Axl 表达的抑制可调节与细胞存活相关的基因的转录程序，这些基因均与 NF-κB 通路相关。此外，阻断 Axl 表达会抑制 Akt、IKKα 和 IκBα 磷酸化，从而增加 IκBα 表达和稳定性。此外，Axl 敲低细胞中 IGF1 诱导 Akt 磷酸化可恢复 Akt 活性和增殖。总而言之，我们的结果确定了 Axl 在前列腺癌肿瘤发生中的明确作用，并对前列腺癌治疗具有影响。
Deregulation of the receptor tyrosine kinase Axl has been implicated in the progression of several human cancers. However, the role of Axl in prostate cancer remains poorly understood, and the therapeutic efficacy of Axl targeting remains untested. In this report we identified Axl as a new therapeutic target for prostate cancer. Axl is consistently overexpressed in prostate cancer cell lines and human prostate tumors. Interestingly, the blockage of Axl gene expression strongly inhibits proliferation, migration, invasion, and tumor growth. Furthermore, inhibition of Axl expression by small interfering RNA regulates a transcriptional program of genes involved in cell survival, strikingly all connected to the NF-κB pathway. Additionally, blockage of Axl expression leads to inhibition of Akt, IKKα and IκBα phosphorylation, increasing IκBα expression and stability. Furthermore, induction of Akt phosphorylation by IGF1 in Axl knockdown cells restores Akt activity and proliferation. Taken together our results establish an unambiguous role for Axl in prostate cancer tumorigenesis with implications for prostate cancer treatment.