FBXO22 Accelerates Pancreatic Cancer Growth by Deactivation of the Hippo Pathway via Destabilizing LATS2

Background Dysregulation of ubiquitin ligases plays a crucial role in the development and progression of various human tumors. F-box only protein 22 (FBXO22), an F-box E3 ubiquitin ligase, has been reported to participate in diverse aspects of cancer progression. However, the clinical significance and biological function of FBXO22 in pancreatic cancer remain poorly understood.Aims This study aimed to investigate the role of FBXO22 in promoting pancreatic cancer growth.Methods FBXO22 expression was detected in pancreatic cancer and adjacent normal tissues using qRT-PCR, western blot-ting, and immunohistochemistry. Ectopic expression and knockdown of FBXO22 were performed to measure the impact on pancreatic cancer cells growth by CCK-8, colony formation, and tumorigenicity assay. Bioinformatics analysis uncovered the potential correlation between FBXO22 and various signaling pathways. Western blotting and immunoprecipitation were performed to identify FBXO22-interacting proteins.Results We observed that FBXO22 was upregulated in samples obtained from patients with pancreatic cancer compared with its levels in the adjacent normal tissues, and an elevated FBXO22 level was obviously associated with poor prognosis among patients with pancreatic cancer. FBXO22 knockdown impaired pancreatic cancer cell growth both in vitro and in vivo, whereas FBXO22 overexpression accelerated pancreatic cancer cell growth. Furthermore, we found that FBXO22 contrib-uted to pancreatic cancer cell growth by deactivating the Hippo pathway. Mechanistically, FBXO22 directly interacts with and destabilizes the large tumor suppressor 2 (LATS2), which is a critical regulator of the Hippo pathway. Blocking LATS2 leads to the loss of FBXO22-mediated oncogenic effect in pancreatic cancer.Conclusions These findings provide new insights into the upstream regulation of the Hippo pathway inactivation in pancreatic cancer growth and identify FBXO22 as a potential therapeutic target for this lethal malignant tumor.

Automated summary

This study investigates the role of FBXO22 in promoting pancreatic cancer growth. The researchers found that FBXO22 is upregulated in pancreatic cancer tissues and is associated with poor prognosis. Knockdown of FBXO22 inhibits pancreatic cancer cell growth, while overexpression accelerates it. Mechanistically, FBXO22 deactivates the Hippo pathway by directly interacting with and destabilizing LATS2. These findings shed light on the regulation of the Hippo pathway in pancreatic cancer growth and identify FBXO22 as a potential therapeutic target.