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

Xia DA; Han Ge; Junfeng Shi; Chunhua Zhu; Guozhu Wang; Yuan Fang; Jin Xu

doi:10.32604/or.2024.045433

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

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

Authors

Xia DA¹, Han Ge², Junfeng Shi³, Chunhua Zhu¹, Guozhu Wang¹, Yuan Fang⁴, Jin Xu¹

Affiliations

¹ Department of Breast and Thyroid, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
² Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
³ Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
⁴ Department of Pathology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.

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.

Keywords: Apoptosis; Metastasis; PI3K/AKT/mTOR signaling; Proliferation; Receptor tyrosine kinase-like orphan receptor 2; Triplet-negative breast cancer.

MeSH terms

Cell Line, Tumor
Cell Movement*
Doxorubicin / pharmacology
Drug Resistance, Neoplasm* / genetics
Female
Gene Expression Regulation, Neoplastic
Humans
Neoplasm Invasiveness*
Phosphatidylinositol 3-Kinases* / metabolism
Proto-Oncogene Proteins c-akt* / metabolism
Receptor Tyrosine Kinase-like Orphan Receptors* / genetics
Receptor Tyrosine Kinase-like Orphan Receptors* / metabolism
Signal Transduction*
TOR Serine-Threonine Kinases* / metabolism
Triple Negative Breast Neoplasms* / genetics
Triple Negative Breast Neoplasms* / metabolism
Triple Negative Breast Neoplasms* / pathology

Substances

Receptor Tyrosine Kinase-like Orphan Receptors
TOR Serine-Threonine Kinases
Proto-Oncogene Proteins c-akt
ROR2 protein, human
Phosphatidylinositol 3-Kinases
MTOR protein, human
Doxorubicin