Identification of <scp>calmodulin‐like</scp> protein 5 as tumor‐suppressor gene silenced during early stage of carcinogenesis in squamous cell carcinoma of uterine cervix

Abstract In the course of identifying molecular mechanism that is related to strong cell‐cell adhesion in stratified structures squamous epithelium, calmodulin‐like protein 5 (CALML5) was identified as a spinous structure‐associated by producing monoclonal antibodies with use crude intercellular portion tissue an immunogen and subsequent morphologic screening. By electrophoretic mobility shift assay (EMSA) series mutagenesis studies, two transcription factors, ZNF750 KLF4, binding line CALML5 gene promoter, were found play central role transcription. Knockdown siRNA A431 cell expresses high levels resulted acceleration wound confluence scratch assay, indicating functions tumor‐suppressor uterine cervical cancer. Immunohistochemical evaluation intraepithelial lesions, carcinoma situ (CIS) invasive cancer, revealed reduction expression during stages CIS through various pathways including blockage nuclear translocation KLF4. Conversely, restoration KLF4 inhibiting ERK‐signaling reactivated ME180 cells expressing low CALML5. Thus, alteration p63‐ZNF750‐KLF4 axis may result critical functional loss CALM‐related genes cancer progression. Although morphological association spiny‐structure relation motility not clear, provides useful diagnostic indicator differentiating dysplasia, preinvasive cancers.