Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0476089 (endometrial cancer)
 11,379 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although platinum drugs are often used for the chemotherapy of human cancers, platinum resistance is a major issue and may preclude their use in some cases. We recently reported that enhanced expression of Annexin A4 (Anx A4) increases chemoresistance to carboplatin through increased extracellular efflux of the drug. However, the precise mechanisms underlying that chemoresistance and the relationship of Anx A4 to platinum resistance in vivo remain unclear. In this report, the in vitro mechanism of platinum resistance induced by Anx A4 was investigated in endometrial carcinoma cells (HEC1 cells) with low expression of Anx A4. Forced expression of Anx A4 in HEC1 cells resulted in chemoresistance to platinum drugs. In addition, HEC1 control cells were compared with Anx A4-overexpressing HEC1 cells in xenografted mice. Significantly greater chemoresistance to cisplatin was observed in vivo in Anx A4-overexpressing xenografted mice. Immunofluorescence analysis revealed that exposure to platinum drugs induced relocation of Anx A4 from the cytoplasm to the cellular membrane, where it became colocalized with ATP7A, a copper transporter also well known as a mechanism of platinum efflux. ATP7A expression suppressed by small interfering RNA had no effect on HEC1 control cells in terms of chemosensitivity to platinum drugs. However, suppression of ATP7A in Anx A4-overexpressing platinum-resistant cells improved chemosensitivity to platinum drugs (but not to 5-fluorouracil) to a level comparable to that of control cells. These results indicate that enhanced expression of Anx A4 confers platinum resistance by promoting efflux of platinum drugs via ATP7A.
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PMID:Annexin A4-conferred platinum resistance is mediated by the copper transporter ATP7A. 2415 Sep 77

Annexin A4 (Anxa4) is one of the Ca(2+)-regulated and phospholipid-binding annexin superfamily proteins. Anxa4 has a potential role in diagnosis, prognosis, and treatment of certain cancers. Studies indicate that Anxa4 up-regulation promotes the progression of tumor and chemoresistance of colorectal cancer (CRC), esophageal squamous cell carcinoma (ESCC), endometrial carcinoma (EC), gastric cancer (GC), chemoresistant lung cancer (LC), malignant mesothelioma (MM), renal cell carcinoma (RCC), ovarian clear cell carcinoma (OCCC), cholangiocarcinoma, hepatocellular carcinoma (HCC), breast cancer (BC), and laryngeal cancer. Interestingly, Anxa4 also might specifically function as a tumor suppressor for prostate cancer (PCa) and have a paradoxical role for pancreatic cancer (PCC). Differential expression of Anxa4 may distinguish major salivary gland tumor (MSGT) from thyroid cancer. In addition, its differential expression was linked to Sirt1-induced cisplatin resistance of oral squamous cell carcinoma (OSCC) and miR-7-induced migration and invasion inhibition of glioma. This current review summarizes and discusses the clinical significance of Anxa4 in cancer as well as its potential mechanisms of action. It may provide new integrative understanding for future studies on the exact role of Anxa4 in cancer.
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PMID:Annexin A4 and cancer. 2604 90