Protein Tyrosine Kinase 7 Regulates EGFR/Akt Signaling Pathway and Correlates With Malignant Progression in Triple-Negative Breast Cancer

PurposeTriple-negative breast cancer (TNBC), the most aggressive subtype of breast cancer, is associated with high invasiveness, high metastatic occurrence and poor prognosis. Protein tyrosine kinase 7 (PTK7) plays an important role in multiple cancers. However, the role of PTK7 in TNBC has not been well addressed. This study was performed to evaluate the role of PTK7 in the progression of TNBC.MethodsCorrelation of PTK7 expression with clinicopathological parameters was assessed using tissue microarray immunohistochemistry (IHC) staining in 280 patients with breast cancer. PTK7 expression in TNBC (MDA-MB-468, MDA-MB-436 and MDA-MB-231) and non-TNBC (MCF7 and SK-BR-3) breast cancer cell lines were examined using immunoblotting assay. PTK7 correlated genes in invasive breast carcinoma were analyzed using cBioPortal breast cancer datasets including 1,904 patients. PTK7 overexpressed or knockdown TNBC cell lines (MDA-MB-468 and MDA-MB-436) were used to analyze the potential roles of PTK7 in TNBC metastasis and tumor progression. A TNBC tumor bearing mouse model was established to further analyze the role of PTK7 in TNBC tumorigenicity in vivo.ResultsPTK7 is highly expressed in breast cancer and correlates with worse prognosis and associates with tumor metastasis and progression in TNBC. Co-expression analysis and gain- or loss-of-function of PTK7 in TNBC cell lines revealed that PTK7 participates in EGFR/Akt signaling regulation and associated with extracellular matrix organization and migration genes in breast cancer, including COL1A1, FN1, WNT5B, MMP11, MMP14 and SDC1. Gain- or loss-of-function experiments of PTK7 suggested that PTK7 promotes proliferation and migration in TNBC cell lines. PTK7 knockdown MDA-MB-468 cell bearing mouse model further demonstrated that PTK7-deficiency inhibits TNBC tumor progression in vivo.ConclusionThis study identified PTK7 as a potential marker of worse prognosis in TNBC and revealed PTK7 promotes TNBC metastasis and progression via EGFR/Akt signaling pathway.

Multi-carbon dots and aptamer based signal amplification ratiometric fluorescence probe for protein tyrosine kinase 7 detection

Background Protein tyrosine kinase 7 (PTK 7) is a membrane receptor, which can be found in various kinds of cancers. In view of this, detection of PTK 7 in the peripheral circulation would be an effective way for the early diagnosis of cancer. Results In this work, a multi-carbon dots and aptamer-based signal amplification ratiometric fluorescence probe was developed. The fluorescence of the aptamer-modified y-CDs and b-CDs were respectively chosen as the detection signal and interior label. The fluorescence of y-CDs was quenched by Fe3O4 and cDNA (complement to aptamer) compound without PTK 7, but recovered by the addition of PTK 7. Then, the free aptamer was cut by DNase I, which amplified the detection signal. The ratiometric fluorescence sensor for PTK 7 was established with the LOD of 0.016 ng mL−1. Conclusions Summary, a multi-carbon dots and aptamer-based signal amplification ratiometric fluorescence probe was developed for the detection of protein tyrosine kinase 7. The developed probe was applied to PTK 7 detection in MCF-7 cells and human serum with satisfying results, thus indicating that this probe has huge potential in clinical practice.

Multi-Carbon Dots and Aptamer Based Signal Amplification Ratiometric Fluorescence Probe for Protein Tyrosine Kinase 7 Detection

Background: Protein tyrosine kinase 7 (PTK 7) is a membrane receptor, whichcan be found in various kinds of cancers . In view of this, detection of PTK 7 in theperipheral circulation would be an effective way for the early diagnosis of cancer.Results: In this work, a multi carbon dots and aptamer based signal amplificationratiometric fluorescence probe was developed . The fluorescence of the aptamermodified y CDs and b CDs were respectively chosen as the detection signal and interiorlabel The fluorescence of y CDs was quenched by Fe 3 O 4 and cDNA (complement toaptamer) compound without PTK 7 but recovered by the addition of PTK 7. Then, t hefree aptamer was cut by DNase Ⅰ, which amplified the detection signal. The ratiometricfluorescence sensor for PTK 7 was established with the LOD of 0.016 ng mL-1Conclusions: Summary , a multi carbon dots and aptamer based signal amplificationratiometric fluorescence probe was developed for the detection of protein tyrosinekinase 7. The developed probe was applied to PTK 7 detection in MCF 7 cells andhuman serum with satisf ying results, thus indicat ing that this probe ha s huge potentialin clinical practice.

Differential expression of PTK7 in the primary tumors of breast cancer patients treated with trastuzumab.

The mechanism of action underlying trastuzumab (Herceptin) function is thought to be binding of the Fab region of trastuzumab to the extracellular domain of the human epidermal growth factor receptor (HER2) (1). The transcriptional responses that follow signals transduced after trastuzumab binding of HER2 are less well understood. We mined published microarray and multiplexed gene expression data (2-4) to understand in an unbiased fashion genes most differentially expressed in the primary tumors of breast cancer patients treated with trastuzumab. We observed significantly increased and differential expression of the protein tyrosine kinase 7, PTK7 (5-7).

The Development of Electrochemical Aptasensor Based on DNA Aptamers Modified by Redox Markers for Detection of Leukemia Jurkat Cells

Oncological diseases belong to the most serious illnesses with high mortality. The most common cancer in children is acute lymphoblastic leukemia (ALL). It is important to develop diagnostic methods that will be able to detect this disease in early stage. One of the possible options can be non-invasive diagnostics using the biosensors based on nucleic acid aptamers. Aptamer recognizes the surface markers on the membrane of cancer cells with the high binding affinity. Biosensors based on aptamers with redox markers are among the most sensitive experimental tools of this type. We developed and optimized the redox-labeled electrochemical aptasensors for the detection of Jurkat leukemia cells. The aptamers specific to the protein tyrosine kinase 7 (PTK7), which is important membrane protein cancer marker that is overexpressed in Jurkat cells were used. We compared the sensitivity of aptasensors for aptamers modified either by methylene blue (MB) and ferrocene carboxylic acid (Fc), respectively. Both aptasensors were tested in the presence of Jurkat cells at concentration range 50–5000 cells/mL using differential pulse voltammetry. In both cases the comparable sensitivity was obtained with limit of detection: 37 ± 6 cells/mL for Fc-labeled aptamers and 38 ± 8 cells/mL for MB-labeled aptamers based on 3.3S/N (signal to noise) rule. The interaction of the sensing surface with control U266 cells was less significant.