ABRC, School of Life Sciences, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University, Daegu 702-701, South Korea.
Aquaculture Management Division, National Fisheries Research and Development Institute, Busan 619-705, South Korea.
Biochem Biophys Res Commun. 2014 Jul 18;450(1):659-65. doi: 10.1016/j.bbrc.2014.06.027. Epub 2014 Jun 14.
Members of the Eph family have been implicated in the formation of cell-cell boundaries, cell movement, and positioning during development in the context of cancer progression. De-regulation of this signaling system is linked to the promotion of more aggressive and metastatic tumor phenotypes in a large variety of human cancers, including breast, lung, and prostate cancer, melanoma, and leukemia. Thus, it is interesting to consider the case of cancer progression where de-regulation of the Eph/ephrin signaling system results in invasion and metastasis. Here, we present evidence that Pick1, one of the essential components of the adherens junction, recovers ephrinB1-induced cell-cell de-adhesion. Loss of Pick1 leads to dissociation of epithelial cells via disruption of the adherens junction, a phenotype similar to ephrinB1 overexpression. In addition, overexpressed ephrinB1-induced disruption of the adherens junction is rescued via binding to Pick1. These data indicate that Pick1 is involved in regulating the cell-cell junction in epithelial cells, and this may influence therapeutic strategy decisions with regards to cell adhesion molecules in metastatic disease.
Eph 家族成员已被牵涉到细胞-细胞边界的形成、细胞运动以及在癌症进展过程中的定位。该信号系统的失调与更具侵袭性和转移性的肿瘤表型的促进有关，这在多种人类癌症中都有发现，包括乳腺癌、肺癌和前列腺癌、黑色素瘤和白血病。因此，在考虑癌症进展的情况下，Eph/ephrin 信号系统的失调会导致侵袭和转移是很有趣的。在这里，我们提出证据表明，黏着连接的必需组成部分之一 Pick1 可以恢复 ephrinB1 诱导的细胞-细胞去黏附。Pick1 的缺失会导致上皮细胞通过破坏黏着连接而解离，这一表型类似于 ephrinB1 的过表达。此外，通过与 Pick1 结合，过表达的 ephrinB1 诱导的黏着连接破坏可以得到挽救。这些数据表明，Pick1 参与调节上皮细胞中的细胞-细胞连接，这可能会影响转移性疾病中细胞黏附分子的治疗策略决策。
