Esophageal squamous cell carcinoma (ESCC) is a common subtype of esophageal cancer that is particularly prevalent in East Asian countries. Our previous expression profile analysis showed that the gene encoding protein tyrosine kinase 7 (PTK7) is upregulated in ESCC tissues. Here, we aimed to validate PTK7 as a prognostic factor and a candidate target for molecular treatment of ESCC. Both RT-PCR and Western blot analysis of tissues from ESCC patients revealed that PTK7 was significantly upregulated in tumor tissue samples of ESCC. Immunohistochemical staining of PTK7 showed that increased expression of PTK7 was inversely correlated with overall survival (P = 0.021). In vitro knockdown of PTK7 inhibited proliferation, survival, wound healing, and invasion of ESCC cells. In addition, PTK7 knockdown decreased phosphorylation of Akt, Erk, and focal adhesion kinase (FAK), important determinants of cell proliferation, survival, and migration. Therefore, our findings suggest that PTK7 has potential as a prognostic marker for ESCC and might also be a candidate for targeted therapy in the treatment of ESCC. (Cancer Sci 2013; 104: 1120-1126 E sophageal cancer is one of the most devastating malignancies. Despite recent developments in its management, advanced esophageal cancer is associated with high rates of local recurrence and distant metastasis.(1,2) Although there has been improvement in clinical outcome through multidisciplinary treatment strategies, (3)(4)(5) such as total mediastinal lymph node dissection, (6) and new diagnostic modalities such as positron emission tomography, (7) these developments have not proven satisfactory in preventing the high recurrence rates. Currently, the prognosis is only promising if the tumor is detected early and resected completely.Esophageal squamous cell carcinoma (ESCC) is the most common histologic subtype of esophageal cancer in East Asian countries.(8) It has a unique profile of clinical and anatomical characteristics that is distinct from those of esophageal adenocarcinoma, which is more prevalent in North America, UK, and Australia.(8) To develop prognostic diagnosis and effective therapeutics for ESCC, the identification of biomarkers is of vital importance. In a gene expression profiling analysis to pursue biomarkers, we identified protein tyrosine kinase 7 (PTK7; also known as colon carcinoma kinase-4 or CCK-4), as a candidate biomarker for ESCC. (9) Protein tyrosine kinase 7 is a receptor tyrosine kinase-like molecule containing an extracellular domain with seven immunoglobulin-like loops, a transmembrane domain, and a defective tyrosine kinase domain that resembles a catalytic domain but lacks catalytic activity.(10-12) Mice expressing a truncated form of PTK7 protein die perinatally, revealing a defect in neural tube closure and stereociliary bundle orientation. These findings implicate PTK7 as a regulator of planar cell polarity (PCP).(13) It has been shown that PTK7 recruits RACK1, which affects Dsh recruitment by interaction with PKCd1. (14) Interaction between PTK7...