Department of Pathology, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan Province, People's Republic of China; Department of Pathology, Southwest Medical University, Luzhou 646000, Sichuan Province, People's Republic of China.
Department of Pathology, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan Province, People's Republic of China; Department of gastroenterology, The People' Hospital of Leshan, Leshan 644000, Sichuan Province, People's Republic of China; Precision Pathology Diagnosis for Serious Diseases Key Laboratory of Luzhou, Luzhou 646000, Sichuan Province, People's Republic of China.
Pathol Res Pract. 2023 Dec;252:154921. doi: 10.1016/j.prp.2023.154921. Epub 2023 Nov 4.
Breast 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.
Immunohistochemistry 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.
DNAJA1 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 and reduced its degradation. Up regulation of DNAJA1 in mutant P53 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.
Our study reveals that DNAJA1 is up regulated in breast cancer and promotes breast cancer cells proliferation and metastasis via P53/NF-κB pathway. It might be a potential prognosis marker for the breast cancer patients.
乳腺癌是最常见的恶性肿瘤之一，具有较高的转移性和转移率。DNAJA1 与几种肿瘤的肿瘤进展密切相关。然而，DNAJA1 在乳腺癌转移和增殖中的作用和机制尚不清楚。
采用免疫组织化学和 Western blot 检测蛋白表达基因。进行体内和体外实验，评估乳腺癌细胞的增殖、侵袭和转移能力。
在 234 例乳腺癌组织中，DNAJA1 高表达，与转移、p53 表达和患者生存不良相关。DNAJA1 敲低可减少乳腺癌细胞平板克隆形成的数量和 CCK8 测定的 OD 值。DNAJA1 的耗竭也降低了乳腺癌细胞的侵袭能力。在体内，敲低 DNAJA1 可减少皮下肿瘤和肺转移灶的生长。在机制上，DNAJA1 可以与 P53 结合并减少其降解。突变型 P53 乳腺癌细胞中 DNAJA1 的上调促进了 p65 的核易位，激活了 NF-κB 通路，并增强了其下游基因如 MMP9、CXCL10 等的转录。NF-κB 通路的阻断可有效挽救 DNAJA1 对乳腺癌细胞增殖和转移的影响。
我们的研究表明，DNAJA1 在乳腺癌中上调，并通过 P53/NF-κB 通路促进乳腺癌细胞的增殖和转移。它可能是乳腺癌患者的一个潜在预后标志物。
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