PTPRA facilitates cancer growth and migration via the TNF‑α‑mediated PTPRA‑NF‑κB pathway in MCF‑7 breast cancer cells

Abstract

Protein tyrosine phosphatase receptor type A (PTPRA), one of the classic protein tyrosine phosphatases, is crucial for modulating tumorigenesis and metastasis in breast cancer; however, its functional mechanism has not fully elucidated. The present study assessed PTPRA expression and estimated its clinical impact on survival using the Gene Expression Profiling Interactive Analysis database (GEPIA). Growth curves, colony formations and Transwell assays were utilized to examine cell proliferation and migration. Additionally, luciferase reporter assays were used to examine the potential tumor signaling pathways targeted by PTPRA in HEK293T cells. Furthermore, quantitative PCR (qPCR) was utilized to confirm the transcriptional regulation of PTPRA expression. Bioinformatic analyses of data from GEPIA identified PTPRA overexpression in patients with breast cancer. The growth curve, colony formation and transwell experiments demonstrated that PTPRA upregulation significantly promoted the cell proliferation and migration of MCF-7 breast cancer cells. In contrast, PTPRA knockdown significantly attenuated cell proliferation and migration. Mechanistic experiments revealed that the transcriptional activity of NF-κB was higher compared with other classic tumor pathways when they were activated by PTPRA in HEK293T cells. Furthermore, the transcriptional activity of NF-κB was altered in a PTPRA-dose-dependent manner. Additionally, following exposure to TNF-α, PTPRA-deficient MCF-7 cells exhibited lower NF-κB transcriptional activity compared with normal control cells. The results of the present study demonstrate that PTPRA overexpression accelerates inflammatory tumor phenotypes in breast cancer and that the TNF-α-mediated PTPRA-NF-κB pathway may offer novel insight into early diagnosis and optimum treatment for breast cancer.

Identification of orphan ligand-receptor relationships using a cell-based CRISPRa enrichment screening platform

“…PTPRA also associates with RET signaling complexes and can directly dephosphorylate RET, causing inhibition of RET signaling ( Yadav et al, 2020 ). Elevated levels of PTPRA leads to promotion of lung cancer and is associated with poor prognosis and overall survival ( Gu et al, 2017 ; Lin et al, 2020 ) through c-Src activation. PTPRA has not been demonstrated to directly bind to RET, however, and a linkage between PTPRA and RET might be provided by GAS1.…”

Clustering of phosphatase RPTPα promotes Src signaling and the arthritogenic action of synovial fibroblasts

“…Cells were lysed in radioimmunoprecipitation assay (RIPA) buffer (Cell Signaling Technology, 9806S) containing protease and phosphatase inhibitor (Thermo Fisher Scientific, A32961), and lysates were sonicated and centrifuged (13,200 rpm at 4°C for 20 min). The samples were resuspended in SDS denaturing buffer (1× Laemmli sample buffer, 5% β-mercaptoethanol, and 2.05% SDS) and loaded onto SDS-polyacrylamide gel electrophoresis gels.…”

“…The interaction between the SRC homology 2 (SH2) domain of SRC and a phosphorylation Tyr 789 (Tyr 825 in the isoform used in this work) residue in the D2 domain of RPTPα reportedly promotes formation of such a complex ( 10 ), although it remains to be clarified whether this is the only mechanism ( 11 ). RPTPα is overexpressed in several cancers and is considered a therapeutic target to reduce activation of SRC and cancer cell growth ( 12 , 13 ). RPTPα also plays an important role in the pathogenic action of fibroblast populations.…”

MicroRNAs regulating SOX2 in cancer progression and therapy response

“…Furthermore, TNF- α enhances NF- κ B expression to promote breast cancer proliferation (Ref. 265). Interestingly, TNF- α can affect SOX2 expression via targeting miRNAs.…”

“…ID4 can trigger chemoresistance of breast cancer cells via enhancing activity of drug transporters (Ref. 265). In glioma cells, miRNA-9 suppresses SOX2 expression to induce chemoresistance and cancer stemness.…”