PTK 7 Is a Transforming Gene and Prognostic Marker for Breast Cancer and Nodal Metastasis Involvement

Abstract

Protein Tyrosin Kinase 7 (PTK7) is upregulated in several human cancers; however, its clinical implication in breast cancer (BC) and lymph node (LN) is still unclear. In order to investigate the function of PTK7 in mediating BC cell motility and invasivity, PTK7 expression in BC cell lines was determined. PTK7 signaling in highly invasive breast cancer cells was inhibited by a dominant-negative PTK7 mutant, an antibody against the extracellular domain of PTK7, and siRNA knockdown of PTK7. This resulted in decreased motility and invasivity of BC cells. We further examined PTK7 expression in BC and LN tissue of 128 BC patients by RT-PCR and its correlation with BC related genes like HER2, HER3, PAI1, MMP1, K19, and CD44. Expression profiling in BC cell lines and primary tumors showed association of PTK7 with ER/PR/HER2-negative (TNBC-triple negative BC) cancer. Oncomine data analysis confirmed this observation and classified PTK7 in a cluster with genes associated with agressive behavior of primary BC. Furthermore PTK7 expression was significantly different with respect to tumor size (ANOVA, p = 0.033) in BC and nodal involvement (ANOVA, p = 0.007) in LN. PTK7 expression in metastatic LN was related to shorter DFS (Cox Regression, p = 0.041). Our observations confirmed the transforming potential of PTK7, as well as its involvement in motility and invasivity of BC cells. PTK7 is highly expressed in TNBC cell lines. It represents a novel prognostic marker for BC patients and has potential therapeutic significance.

In silico DNA methylation analysis identifies potential prognostic biomarkers in type 2 papillary renal cell carcinoma

“…PTK7 is an intrinsic component of the Wnt pathway and a member of the receptor tyrosine kinase family . In multiple cancers including esophageal squamous cell carcinoma, intrahepatic cholangiocarcinoma, breast cancer, and prostate cancer, PTK7 is overexpressed and inversely correlated with overall survival . Copy number gain in PTK7 is associated with increased gene expression, which is also observed in gastric cancer .…”

Therapeutic Targeting of PTK7 is Cytotoxic in Atypical Teratoid Rhabdoid Tumors

“…Knockdown of PTK7 resulted in significantly decreased viability of ATRT cell lines, suggesting that PTK7 may be involved in tumor cell growth and proliferation. In multiple cancer types, such as colon cancer, gastric cancer, breast cancer, and acute myeloid leukemia, high PTK7 levels are correlated to poor drug response, increased metastasis, and poor patient survival rates (15,19,41–43). The role of PTK7 in different cancers is not yet known, but it is thought that PTK7 may promote tumorigenesis as expression of PTK7 in leukemia cells enhances cell migration and survival (19).…”

Protein-tyrosine Pseudokinase 7 (PTK7) Directs Cancer Cell Motility and Metastasis

“…As a result, the literature suggests that the expression of PTK7 is up-regulated in colon (23,24), gastric (25) and lung cancers, and acute myeloid leukemia (26,27) and down-regulated in melanomas (28,29) and breast carcinomas (30,31), some of which exhibit deletions of the human chromosome 6p containing the genomic PTK7 gene. The most recent observations by others suggest the fundamental function and the high prognostic value of PTK7 in the most aggressive, metastatic cancer types, including breast, lung, and colorectal cancer and intrahepatic cholangiocarcinoma (32)(33)(34)(35).…”