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Abstract：
The PAR clan of polarity regulating genes was initially discovered in a genetic screen searching for genes involved in asymmetric cell divisions in the Caenorhabditis elegans embryo. Today, investigations in worms, flies and mammals have established PAR proteins as conserved and fundamental regulators of animal cell polarization in a broad range of biological phenomena requiring cellular asymmetries. The human homologue of invertebrate PAR-4, a serine-threonine kinase LKB1/STK11, has caught attention as a gene behind Peutz-Jeghers polyposis syndrome and as a bona fide tumour suppressor gene commonly mutated in sporadic cancer. LKB1 functions as a master regulator of AMP-activated protein kinase (AMPK) and 12 other kinases referred to as the AMPK-related kinases, including four human homologues of PAR-1. The role of LKB1 as part of the energy sensing LKB1-AMPK module has been intensively studied, whereas the polarity function of LKB1, in the context of homoeostasis or cancer, has gained less attention. Here, we focus on the PAR-4 identity of LKB1, discussing the weight of evidence indicating a role for LKB1 in regulation of cell polarity and epithelial integrity across species and highlight recent investigations providing new insight into the old question: does the PAR-4 identity of LKB1 matter in cancer?
摘要：
极性调节基因的PAR家族最初是在基因筛选中发现的，该基因在秀丽隐杆线虫胚胎中寻找参与不对称细胞分裂的基因。今天,对蠕虫的调查，果蝇和哺乳动物已经建立了PAR蛋白作为动物细胞极化的保守和基本调节剂，在需要细胞不对称的广泛生物学现象中。无脊椎动物PAR-4的人类同源物，一种丝氨酸-苏氨酸激酶LKB1/STK11，已作为Peutz-Jeghers息肉病综合征背后的基因以及在散发性癌症中通常突变的真正的肿瘤抑制基因引起了人们的注意。LKB1作为AMP激活的蛋白激酶（AMPK）和12种其他称为AMPK相关激酶的激酶的主要调节因子，包括四个PAR-1的人类同源物。LKB1作为能量传感LKB1-AMPK模块的一部分的作用已被深入研究,而LKB1的极性功能，在同质性或癌症的背景下，受到的关注较少。这里,我们专注于LKB1的PAR-4身份，讨论表明LKB1在调节跨物种的细胞极性和上皮完整性中起作用的证据的权重，并强调最近的研究提供了对旧问题的新见解：LKB1的PAR-4身份在癌症中是否重要？
