CIB1 is a homolog of calmodulin that regulates cell adhesion, migration, and differentiation. It has been considered as an oncogene in many tumor cells; however, its role in lung adenocarcinoma (LAC) has not been studied. In this study, the expression levels of CIB1 in LAC tissues and adjacent normal tissues were examined by immunohistochemistry, and the relationship between CIB1 expression and patient clinicopathological characteristics was analyzed. The effects of CIB1 on epithelial–mesenchymal transition (EMT), migration, and metastasis of LAC cells were determined in vitro and vivo. Proteins interacting with CIB1 were identified using electrospray mass spectrometry (LS-MS), and CHIP was selected in the following assays. Carboxyl-terminus of Hsp70-interacting protein (CHIP) is a ubiquitin E3 ligase. We show that CHIP can degrade CIB1 via promoting polyubiquitination of CIB1 and its subsequent proteasomal degradation. Besides, lysine residue 10 and 65 of CIB1 is the ubiquitinated site of CIB1. Furthermore, CHIP-mediated CIB1 downregulation is critical for the suppression of metastasis and migration of LAC. These results indicated that CHIP-mediated CIB1 ubiquitination could regulate epithelial–mesenchymal and tumor metastasis in LAC.

CIB1 是调节细胞粘附、迁移和分化的钙调蛋白的同源物。它被认为是许多肿瘤细胞中的致癌基因；然而，尚未研究其在肺腺癌 (LAC) 中的作用。本研究采用免疫组化方法检测 LAC 组织及邻近正常组织中 CIB1 的表达水平，分析 CIB1 表达与患者临床病理特征的关系。在体外和体内测定了 CIB1 对 LAC 细胞上皮间质转化 (EMT)、迁移和转移的影响。使用电喷雾质谱 (LS-MS) 鉴定与 CIB1 相互作用的蛋白质，并在以下测定中选择 CHIP。Hsp70 相互作用蛋白 (CHIP) 的羧基末端是一种泛素 E3 连接酶。我们表明，CHIP 可以通过促进 CIB1 的多泛素化及其随后的蛋白酶体降解来降解 CIB1。此外，CIB1的赖氨酸残基10和65是CIB1的泛素化位点。此外，CHIP 介导的 CIB1 下调对于抑制 LAC 的转移和迁移至关重要。这些结果表明，CHIP 介导的 CIB1 泛素化可以调节 LAC 中的上皮间充质和肿瘤转移。