Sam68 通过诱导 EphA3 的激活促进人乳腺癌的进展。

Sam68 Promotes the Progression of Human Breast Cancer through inducing Activation of EphA3.

机构信息

Department of Breast Surgery, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China.

Department of Breast Surgery, Huadu District People's Hospital of Guangzhou, Guangdong, China.

出版信息

Curr Cancer Drug Targets. 2020;20(1):76-83. doi: 10.2174/1568009619666190718124541.

DOI:10.2174/1568009619666190718124541

PMID:31433759

Abstract

BACKGROUND

Src associated with mitosis of 68 kDa (Sam68), is often highly expressed in human cancers. Overexpression of Sam68 has been shown to be correlated with poor survival prognosis in some cancer patients. However, little is known whether Sam68 plays a role in promoting metastasis in breast cancer.

MATERIALS AND METHODS

The expression of Sam68 protein in breast cancer tissue was detected by immunohistochemistry. Trans-well assay, wound-healing, real-time PCR and Western blotting analysis were used to detect the effect of Sam68 on promoting EMT or metastasis of breast cancer. Next-generation RNA sequencing was used to analyze genes that may be regulated by Sam68.

RESULTS

Sam68 plays a positive role in promoting breast cancer metastasis. Sam68 was found to be overexpressed in breast cancer along with lymph node metastasis. MMP-9 was also found to be overexpressed in breast cancer tissue and was correlated to the expression of Sam68 (P<0.01). Xenograft in NOD/SCID mice and in vitro experiments confirmed that the invasion and metastatic ability of breast cancer cells were regulated by Sam68. And EPHA3 could be up-regulated by Sam68 in breast cancer.

CONCLUSION

High expression of Sam68 participates in breast cancer metastasis by up-regulating the EPHA3 gene.

摘要

背景

Src 与有丝分裂相关的 68 kDa（Sam68）在人类癌症中常高度表达。Sam68 的过表达已被证明与一些癌症患者的不良生存预后相关。然而，尚不清楚 Sam68 是否在促进乳腺癌转移中发挥作用。

材料与方法

免疫组织化学检测乳腺癌组织中 Sam68 蛋白的表达。Trans-well 测定、划痕愈合、实时 PCR 和 Western blot 分析用于检测 Sam68 对促进 EMT 或乳腺癌转移的作用。下一代 RNA 测序用于分析可能受 Sam68 调控的基因。

结果

Sam68 在促进乳腺癌转移中发挥积极作用。Sam68 在乳腺癌中随着淋巴结转移而过度表达。MMP-9 也在乳腺癌组织中过度表达，并与 Sam68 的表达相关（P<0.01）。NOD/SCID 小鼠的异种移植和体外实验证实 Sam68 调节乳腺癌细胞的侵袭和转移能力。Sam68 可以在上调 EPHA3 基因在乳腺癌中表达。