lymphocyte antigen 6 complex locus K (114-133)

In adult male mice, the glycosylphosphatidyl inositol-anchored glycoprotein TEX101 is expressed only in germ cells and is thought to be involved in spermatogenesis. However, the details regarding the function of TEX101 remain to be clarified. We previously identified Ly6k as a candidate TEX101-associated protein, but as molecular probes are not currently available to detect Ly6k, we do not have conclusive evidence of the association between TEX101 and Ly6k. In this study, we confirmed the biological interaction between TEX101 and Ly6k using an established anti-mouse Ly6k polyclonal antibody (pAb). A combination of immunoprecipitation, Western blot, and immunohistochemical analyses using the pAb revealed that TEX101 is physically associated with Ly6k within the testis. In addition, these proteins simultaneously co-migrate into the detergent-resistant membrane fractions, suggesting that TEX101 collaborates with Ly6k on the cell membrane and may play a role in spermatogenesis.

Objective: In this paper, we will discuss the structure, function and role of lymphocyte antigen 6 complex locus K (LY6K) in disease model, and highlight the new progress of LY6K in current clinical trials. It provides reference value for future basic research. Background: Cancer is a global public health problem that must be solved. The ability of tumor cells to evade the antitumor immune response makes cancer research and treatment more difficult. LY6K is highly expressed in a variety of cancers, can stimulate the immune system, and has tumor specificity. At present, a large number of vaccines have entered clinical trials. Methods: The PubMed, umin.ac.jp/ctr and Clinical Trials.gov databases were searched for LY6K published literature and clinical trials. The structure and function of LY6K and the current state of research on LY6K in human cancers were discussed to provide reference for further research. Conclusions: The LY6K gene has been shown to be highly expressed in a variety of tumor cells, driving tumorigenesis and progression, and is negatively correlated with poor prognosis in patients. At the same time, LY6K can stimulate the immune response of the body's immune cells. The study of LY6K-related vaccines in clinical trials also suggests that targeting LY6K may be a new direction for tumor immunotherapy.

Gene expression profile analyses of non-small cell lung carcinomas (NSCLC) and esophageal squamous cell carcinomas (ESCC) revealed that lymphocyte antigen 6 complex locus K (LY6K) was specifically expressed in testis and transactivated in a majority of NSCLCs and ESCCs. Immunohistochemical staining using 406 NSCLC and 265 ESCC specimens confirmed that LY6K overexpression was associated with poor prognosis for patients with NSCLC (P = 0.0003), as well as ESCC (P = 0.0278), and multivariate analysis confirmed its independent prognostic value for NSCLC (P = 0.0035). We established an ELISA to measure serum LY6K and found that the proportion of the serum LY6K-positive cases was 38 of 112 (33.9%) NSCLC and 26 of 81 (32.1%) ESCC, whereas only 3 of 74 (4.1%) healthy volunteers were falsely diagnosed. In most cases, there was no correlation between serum LY6K and conventional tumor markers of carcinoembryonic antigen (CEA) and cytokeratin 19-fragment (CYFRA 21-1) values. A combined ELISA for both LY6K and CEA classified 64.7% of lung adenocarcinoma patients as positive, and the use of both LY6K and CYFRA 21-1 increased sensitivity in the detection of lung squamous cell carcinomas and ESCCs up to 70.4% and 52.5%, respectively, whereas the false positive rate was 6.8% to 9.5%. In addition, knocked down of LY6K expression with small interfering RNAs resulted in growth suppression of the lung and esophageal cancer cells. Our data imply that a cancer-testis antigen, LY6K, should be useful as a new type of tumor biomarker and probably as a target for the development of new molecular therapies for cancer treatment.