DJ-1 activates the noncanonical NF-κB pathway via interaction with Cezanne to inhibit the apoptosis and promote the proliferation of Ishikawa cells

Abstract

Endometrial cancer is generally one of the most evident malignant tumours of the female reproductive system, and the mechanisms underlying its cell proliferation and apoptosis are key to research in gynaecological oncology. In the paper, the in-depth molecular mechanism by which DJ-1 protein regulates the proliferation and apoptosis of Ishikawa cells was investigated. DJ-1 knockdown and overexpressing Ishikawa stable cell lines were established by lentiviral transduction. The levels of DJ-1 and noncanonical NF-κB signaling proteins were evaluated by Western blotting. Cell counting kit-8 (CCK-8) and ow cytometry were applied to analyze the cell viability and apoptosis. Co-immunoprecipitation experiment was utilized to assess the DJ-1-Cezanne interaction. The results showed that DJ-1 overexpression conferred apoptosis resistance and high proliferation on Ishikawa cells, while DJ-1 knockdown in Ishikawa cells produced the opposite results. These ndings again suggested that DJ-1 inhibits the apoptosis and promotes the proliferation of Ishikawa cells. More crucially, further data showed that the noncanonical NF-κB activation was required for the regulation of Ishikawa cell proliferation and apoptosis by DJ-1. Meanwhile, it was found that noncanonical NF-κB pathway may be activated by DJ-1 interacting with and negatively regulating Cezanne in Ishikawa cells. Overall, this work revealed that DJ-1 associates with and negatively regulates Cezanne and consequently triggers the noncanonical NF-κB activation, thereby regulating Ishikawa cell proliferation and apoptosis.

OTUD7B knockdown inhibits the proliferation and stemness of breast cancer cells by destabilizing FOXM1

“…OTUD7B dysregulation has been found to participate in the development of numerous types of cancer, but studies on the role of OTUD7B in oncogenesis have yielded conflicting results. In breast, pancreatic and endometrial cancer, OTUD7B may play an oncogenic role by facilitating the proliferation, progression and metastasis of tumor cells ( 9 , 13 , 26 ). However, in hepatocellular carcinoma (HCC), OTUD7B may function as a tumor suppressor, which is evidenced by the fact that OTUD7B knockdown accelerates the migration and invasion of HCC cells in vitro and promotes metastasis in vivo .…”

Moving beyond the Tip of the Iceberg: DJ-1 Implications in Cancer Metabolism

“…Silencing of DJ-1 in Ishikawa cells causes cell viability inhibition and promotes apoptosis. As suggested by Zhu et al [64], these events are associated with inhibition of the cellular zinc finger anti-NF-κB (Cezanne or OTUD7B) and subsequent activation of the non-canonical NF-κB pathway. Inhibition of Cezanne enables tumor survival through increased expression of IL-8 and ICAM-1 [65].…”