ROR2 通过激活 PI3K/AKT/mTOR 信号促进三阴性乳腺癌细胞的侵袭和化疗耐药性。

ROR2 promotes invasion and chemoresistance of triple-negative breast cancer cells by activating PI3K/AKT/mTOR signaling.

机构信息

Department of Breast and Thyroid, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.

Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

出版信息

Oncol Res. 2024 Jun 20;32(7):1209-1219. doi: 10.32604/or.2024.045433. eCollection 2024.

DOI:10.32604/or.2024.045433

PMID:38948021

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11209745/

Abstract

OBJECTIVE

This study aimed to investigate the role of receptor tyrosine kinase-like orphan receptor 2 (ROR2) in triple-negative breast cancer (TNBC).

METHODS

ROR2 expression in primary TNBC and metastatic TNBC tissues was analyzed by immunohistochemical staining and PCR. ROR2 expression in TNBC cell lines was detected by PCR and Western blot analysis. The migration, invasion and chemosensitivity of TNBC cells with overexpression or knockdown of ROR2 were examined.

RESULTS

ROR2 expression was high in metastatic TNBC tissues. ROR2 knockdown suppressed the migration, invasion and chemoresistance of TNBC cells. ROR2 overexpression in MDA-MB-435 cells promoted the migration, invasion, and chemoresistance. Moreover, ROR2 knockdown in HC1599 and MDA-MB-435 adriamycin-resistant cells enhanced chemosensitivity to adriamycin. ROR2 could activate PI3K/AKT/mTOR signaling in TNBC cells.

CONCLUSION

ROR2 is upregulated and promotes metastatic phenotypes of TNBC by activating PI3K/AKT/mTOR signaling.

摘要

目的

本研究旨在探讨受体酪氨酸激酶样孤儿受体 2（ROR2）在三阴性乳腺癌（TNBC）中的作用。

方法

采用免疫组织化学染色和 PCR 分析原发性 TNBC 和转移性 TNBC 组织中 ROR2 的表达。通过 PCR 和 Western blot 分析检测 TNBC 细胞系中 ROR2 的表达。检测过表达或敲低 ROR2 对 TNBC 细胞迁移、侵袭和化疗敏感性的影响。

结果

ROR2 在转移性 TNBC 组织中高表达。ROR2 敲低抑制了 TNBC 细胞的迁移、侵袭和化疗耐药性。ROR2 在 MDA-MB-435 细胞中的过表达促进了迁移、侵袭和化疗耐药性。此外，HC1599 和 MDA-MB-435 阿霉素耐药细胞中 ROR2 的敲低增强了对阿霉素的化疗敏感性。ROR2 可以在 TNBC 细胞中激活 PI3K/AKT/mTOR 信号通路。