TMEM52B suppression promotes cancer cell survival and invasion through modulating E-cadherin stability and EGFR activity.
TMEM52B suppression promotes cancer cell survival and invasion through modulating E-cadherin stability and EGFR activity.
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TMEM 52 B抑制通过调节E-钙粘蛋白稳定性和EGFR活性促进癌细胞存活和侵袭。
DOI：
10.1186/s13046-021-01828-7
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发表时间：
2021-03-01
期刊：
影响因子：
--
通讯作者：
Kim S
中科院分区：
文献类型：
--
作者：
Lee Y;Ko D;Yoon J;Lee Y;Kim S
TMEM52B是一种在多种正常人体组织中广泛表达的新基因。然而，TMEM52B表达在癌症中的生物学功能在很大程度上是未知的。我们在体外和体内研究了TMEM52B对肿瘤生长和转移的影响，并对其潜在的生物学和分子机制进行了评估。我们分析了来自KmPlotter和癌症基因组图谱（TCGA）的临床数据集与TMEM52B表达和功能的关系。结肠癌细胞中抑制TMEM52B可促进癌细胞上皮-间质转化（EMT）、侵袭和体外存活。同样，体内研究显示肿瘤生长和循环肿瘤细胞存活（早期转移）增加。ERK1/2、JNK和AKT信号通路参与TMEM52B抑制诱导的侵袭性和细胞存活。TMEM52B抑制可促进表皮生长因子受体（EGFR）的激活和内化，增强下游信号活性，从而增强细胞存活和侵袭能力。此外，TMEM52B抑制降低了E-cadherin的稳定性，这可能是由于TMEM52B与E-cadherin之间的关联减少，从而导致β-catenin转录活性增强。同时，TMEM52B抑制促进了可溶性E-cadherin片段的产生，促进了EGFR的激活。临床数据显示，TMEM52B的高表达与乳腺癌、肺癌、肾癌和直肠癌等多种癌症患者的生存率相关，并提示TMEM52B与E-cadherin之间存在相关性。这些发现表明TMEM52B是E-cadherin和EGFR之间相互作用的一种新型调节剂。TMEM52B有可能作为一种肿瘤抑制因子，有可能作为一种新的癌症预后标志物。在线版本包含补充材料，可在10.1186/s13046-021-01828-7获得。
TMEM52B is a novel gene broadly expressed in a variety of normal human tissues. However, the biological function of TMEM52B expression in cancer is largely unknown. The effects of TMEM52B on tumor growth and metastasis were investigated in vitro and in vivo, and the underlying biological and molecular mechanisms involved in this process were evaluated. Clinical datasets from KmPlotter and The Cancer Genome Atlas (TCGA) were analyzed in relation to TMEM52B expression and function. Suppression of TMEM52B in colon cancer cells promoted cancer cell epithelial-mesenchymal transition (EMT), invasion, and survival in vitro. Similarly, in vivo studies showed increased tumor growth and circulating tumor cell survival (early metastasis). ERK1/2, JNK, and AKT signaling pathways were involved in TMEM52B suppression-induced invasiveness and cell survival. TMEM52B suppression promoted activation and internalization of epidermal growth factor receptor (EGFR) with enhanced downstream signaling activity, leading to enhanced cell survival and invasion. In addition, TMEM52B suppression reduced E-cadherin stability, likely due to a reduced association between it and E-cadherin, which led to enhanced β-catenin transcriptional activity. Concomitantly, TMEM52B suppression promoted generation of soluble E-cadherin fragments, contributing to the activation of EGFR. Clinical data showed that high TMEM52B expression correlated with increased patient survival in multiple types of cancer, including breast, lung, kidney, and rectal cancers, and suggested a correlation between TMEM52B and E-cadherin. These findings suggest that TMEM52B is a novel modulator of the interplay between E-cadherin and EGFR. It is possible that TMEM52B functions as a tumor-suppressor that could potentially be used as a novel prognostic marker for cancer. The online version contains supplementary material available at 10.1186/s13046-021-01828-7.
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