肝细胞癌
癌症研究
旁分泌信号
自分泌信号
生物标志物
恶性肿瘤
肿瘤进展
生物
癌症
表型
医学
内科学
受体
基因
生物化学
作者
Zhiwen Gu,Lei Wang,Qian Dong,Kaikun Xu,Jingnan Ye,Xinyi Shao,Songpeng Yang,Cuixiu Lu,Cheng Chang,Yushan Hou,Yuanjun Zhai,Xinxin Wang,Fuchu He,Aihua Sun
标识
DOI:10.1073/pnas.2215744120
摘要
Hepatocellular carcinoma (HCC) takes the predominant malignancy of hepatocytes with bleak outcomes owing to high heterogeneity among patients. Personalized treatments based on molecular profiles will better improve patients’ prognosis. Lysozyme (LYZ), a secretory protein with antibacterial function generally expressed in monocytes/macrophages, has been observed for the prognostic implications in different types of tumors. However, studies about the explicit applicative scenarios and mechanisms for tumor progression are still quite limited, especially for HCC. Here, based on the proteomic molecular classification data of early-stage HCC, we revealed that the LYZ level was elevated significantly in the most malignant HCC subtype and could serve as an independent prognostic predictor for HCC patients. Molecular profiles of LYZ-high HCCs were typical of those for the most malignant HCC subtype, with impaired metabolism, along with promoted proliferation and metastasis characteristics. Further studies demonstrated that LYZ tended to be aberrantly expressed in poorly differentiated HCC cells, which was regulated by STAT3 activation. LYZ promoted HCC proliferation and migration in both autocrine and paracrine manners independent of the muramidase activity through the activation of downstream protumoral signaling pathways via cell surface GRP78. Subcutaneous and orthotopic xenograft tumor models indicated that targeting LYZ inhibited HCC growth markedly in NOD/SCID mice. These results propose LYZ as a prognostic biomarker and therapeutic target for the subclass of HCC with an aggressive phenotype.
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