Androgen receptor is a potential novel prognostic marker and oncogenic target in osteosarcoma with dependence on CDK11

Abstract

Osteosarcoma is the most common bone cancer in children and adolescents. Previously, we have found that cyclin-dependent kinase 11 (CDK11) signaling was essential for osteosarcoma cell growth and survival. Subsequently, CDK11 siRNA gene targeting, expression profiling, and network reconstruction of differentially expressed genes were performed between CDK11 knock down and wild type osteosarcoma cells. Reconstructed network of the differentially expressed genes pointed to the AR as key to CDK11 signaling in osteosarcoma. CDK11 increased transcriptional activation of AR gene in osteosarcoma cell lines. AR protein was highly expressed in various osteosarcoma cell lines and patient tumor tissues. Tissue microarray analysis showed that the disease-free survival rate for patients with high-expression of AR was significantly shorter than for patients with low-expression of AR. In addition, AR gene expression knockdown via siRNA greatly inhibited cell growth and viability. Similar results were found in osteosarcoma cells treated with AR inhibitor. These findings suggest that CDK11 is involved in the regulation of AR pathway and AR can be a potential novel prognostic marker and therapeutic target for osteosarcoma treatment.

CDK11p110 plays a critical role in the tumorigenicity of esophageal squamous cell carcinoma cells and is a potential drug target

“…To further confirm the expression of CDK11 p110 in human ESCC, we determined CDK11 p110 expression in ESCC tissues and adjacent tissues from clinical patients, as well as in a normal esophageal epithelial cell line and six ESCC cell lines, by western blotting. These results indicated that CDK11 p110 was highly expressed in human ESCC tissues and cell lines and were consistent with previous results demonstrating the overexpression of CDK11 p110 in other types of cancer [33,35,36]. For further study, a wider analysis of CDK11 p110 expression in a large cohort of patients with ESCC will be needed to firmly establish whether the expression of CDK11 is correlated with the progression and prognosis of ESCC, as it appears to be for breast cancer.…”

Novel application of single-cell next-generation sequencing for determination of intratumoral heterogeneity of canine osteosarcoma cell lines

“…The androgen receptor pathway expression has been inversely predictive of survival in hOSA. 34 Interestingly, a large 2019 cOSA study 77 found castrated males and spayed bitches had a greater frequency of OSA compared to intact dogs, indicating that sex hormones may play a role in cOSA. Finally, a specific target for aminobisphosphonate drugs, the mevalonate pathway, was also found to be significant in COS31 and DOUG, and is reported to be implicated in the progression of hOSA and cOSA.…”

A Case of a 22-year-Old Man with Primary Synovial Sarcoma of the Parapharyngeal Space with an AR Somatic Mutation: A Clinicopathologic Study and Literature Review

“…To date, AR mutations have shown no clear clinical signi cance in SS. Genetic alterations of AR have been found in prostate cancer [20,21,22] and soft tissue tumours [23,24] in recent years. The androgen receptor gene is located on the X chromosome and it contains a segment of polymorphic CAG tandem repeats in exon 1, and it is an ideal tool to study the clonality of female sarcoma [25], adenomas of the salivary gland [26], and malignant brous histiocytoma [27].…”

“…In vestibular schwannomas, AR is deregulated by a hormonal effect or a change in the tumour microenvironment [23]. AR is key to the CDK11 signalling pathway in osteosarcoma, and patients with high AR expression respond well to preoperative chemotherapy but have a worse 5-year survival [24]. Under certain conditions, AR may serve as a novel therapeutic target in prostate cancer and in some sarcomas.…”