PAK6对前列腺癌的双向调控作用

The bidirectional regulation effect that PAK6 exerts in prostate cancer

前列腺癌为一类男性患病率较高的癌症,对该癌症机制的认识以及治疗手段非常有限,在西欧和美洲男性中是一类致死率较高的癌症。随着科学研究的不断进展,p21活化激酶（PAK）蛋白家族在癌症中发挥的作用开始进入人们的视野。p21活化激酶6（PAK6）最初是以雄激素受体的配体结合域（LBD）上的氨基酸序列629~919,通过酵母双杂交识别出来的雄激素受体相关蛋白。而雄激素与雄激素受体在前列腺癌的发生与发展中发挥了十分重要的作用,因此PAK6蛋白作为前列腺癌治疗的靶向蛋白被不断研究。本文主要介绍PAK6在前列腺癌中的双向调节作用,包括通过磷酸化雄激素受体抑制雄激素受体向核内转移的抑癌作用,和通过抑制BAD凋亡通路、影响前列腺癌细胞生长周期以及促进前列腺癌细胞从细胞集落中脱离的促癌作用。同时PAK6的表达水平和激酶活性的调节对PAK6在前列腺癌中发挥作用具有十分重要的意义。激素与生长因素和内质网应激可能是提高PAK6表达水平和激酶活性的两条途径。PAK6在前列腺癌中发挥的作用与其表达水平和激酶活性的调节机制对前列腺癌的治疗手段以及其治疗药物的靶向目标具有十分重要的意义。

Prostate cancer （PCa）is a type of cancer with high male prevalence.Due to the restrictions of the mecha-nism awareness and limitations of current therapeutic modalities,PCa is the leading diagnosed malignancy in western European and American men.With the continuous progress of scientific research,the role that the PAK protein family play in cancer has been surfaced out of water.PAK6 was primarily an androgen receptor interacting protein recognized by yeast double -hybrid,amino acid sequence 629 919 in ligand binding domain （LBD）of androgen receptor.An-drogen and androgen receptor plays a crucial role in the development and growth of prostate malignancies,which makes PAK6 protein an attractive new therapeutic target in prostate cancer.The article mainly focuses on the double-action that PAK6 takes in PCa,including inhibition of the cancer by phosphorylating AR thus inhibits the AR＇s translocation into nucleus,and promotion of the cancer by inhibiting BAD apoptosis pathway,interfering with growth cycle of PCa cells,and promoting the PCa cells remove from cell colonies.At the same time,the expression level of PAK6 and the regulation of kinase activity also of great significance for PAK6 to affect prostate cancer.This paper ar-gues hormone and growth factor together with reticulum stress are two possible ways in increasing PAK6 expression and im-proving kinase activity.The role PAK6 plays in PCa and the regulatory mechanism between its expression level and ki-nase activity is of great importance to the research of PCa therapeutic modalities and target objectives of medication.