DNAJA1 promotes proliferation and metastasis of breast cancer by activating mutant P53/NF-κB pathway

Abstract

PurposeBreast cancer is one of the most common tumors with high malignancy and metastatic rate. DNAJA1 is closely related to tumor progress in several tumors. However, the role and mechanisms of DNAJA1 in the metastasis and proliferation of breast cancer are unknown. MethodsImmunohistochemistry and western blot were used to detect the protein expression genes. In vivo and vitro experiments were performed to evaluate the proliferation, invasive and metastatic abilities of breast cancer cells. ResultsDNAJA1 was high expressed in 234 cases of breast cancer tissues and associated with metastasis, p53 expression and poor survival for patients. Knock down of DNAJA1 decreased the number of plate clone formation and the OD value of CCK8 assays in breast cancer cells. Depletion of DNAJA1 also in decreased the invasive abilities of breast cancer cells. In vivo, knock down DNAJA1 decreased the growth of subcutaneous tumor and lung metastatic nodes. Mechanically, DNAJA1 could bind with P53-R175H and reduced its degradation. Up regulation of DNAJA1 in mutant P53-R175H breast cancer cell promoted the nuclear translocation of p65, activated NF-κB pathway and enhanced the transcription of its downstream genes such as MMP9, CXCL10 et al. Blockade of NF-κB pathway effectively rescued the effects of DNAJA1 on proliferation and metastasis in breast cancer. ConclusionOur study reveals that DNAJA1 is up regulated in breast cancer and promotes breast cancer cells proliferation and metastasis via P53-R175H/NF-κB pathway. It might be a potential prognosis marker for the breast cancer patients.