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2015年4月16日 讯 /生物谷BIOON/ –近日，一篇发表于国际杂志Cancer Research上的研究报告中，来自Bellvitge生物医学研究所的研究者通过研究发现，名为PARD3的肿瘤抑制子或许在鳞状肺癌类型中是处于失活状态的。
支气管上皮细胞的正确极化对于组织在正常情况下的发育和维持非常必要，极化是细胞的一种空间定位过程；PARD3基因可以编码一种调节细胞极化及细胞连接的蛋白质，当该基因失活时，细胞的定位及其同“邻居”细胞的接触就会发生错误，而影响该蛋白结构的任何改变都将会促进肿瘤的发展。
通过在细胞系及小鼠动物模型机体中恢复PARD3编码的蛋白的水平，研究者就发现，重新调节细胞的极化或许可以明显降低癌症转移的风险。
肺癌是一种在全世界具有较高死亡风险的癌症，仅在西班牙每年就有2万人因肺癌死亡，该病的高死亡率主要是因为疾病诊断较晚，一般当疾病进展到晚期阶段才会被诊断出来。
后期的检测及有效疗法的缺失往往会使得肺癌患者生存的可能性明显降低，总的来讲，在肺癌确诊后仅有10%至15%的患者存活期超过了5年，而80%以上引发患癌的起源都是鼻烟（Snuff）惹得祸，其是发酵烟草粉末加上香料，以鼻吸用的一种烟草制品。鳞状肺癌和肺腺癌是两大肺部肿瘤的常见形式。（基因宝jiyinbao.com）
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PARD3 Inactivation in Lung Squamous Cell Carcinomas Impairs STAT3 and Promotes Malignant Invasion
Ester Bonastre1, Sara Verdura1, Ilse Zondervan2, Federica Facchinetti3, Sylvie Lantuejoul4, Maria Dolores Chiara5, Juan Pablo Rodrigo5, Julian Carretero6, Enric Condom7, Agustin Vidal7, David Sidransky8, Alberto Villanueva9, Luca Roz3, Elisabeth Brambilla4, Suvi Savola2, and Montse Sanchez-Cespedes1,*
Correct apicobasal polarization and intercellular adhesions are essential for the appropriate development of normal epithelia. Here, we investigated the contribution of the cell polarity regulator PARD3 to the development of lung squamous cell carcinomas (LSCC). Tumor-specific PARD3 alterations were found in 8% of LSCCs examined, placing PARD3 among the most common tumor suppressor genes in this malignancy. Most PAR3-mutant proteins exhibited a relative reduction in the ability to mediate formation of tight junctions and actin-based protrusions, bind atypical protein kinase C, activate RAC1, and activate STAT3 at cell confluence. Thus, PARD3 alterations prevented the formation of contacts between neighboring cells and the subsequent downstream signaling. Notably, reconstituting PAR3 activity in vivo reduced tumor-invasive and metastatic properties. Our findings define PARD3 as a recurrently inactivated cell polarity regulator in LSCC that affects tumor aggressiveness and metastasis. Cancer Res; 75(7); 1287–97. ©2015 AACR.