Proteomic analysis reveals LRPAP1 as a key player in the micropapillary pattern metastasis of lung adenocarcinoma
Hao-jie Yan,
Sheng-cheng Lin,
Shao-hang Xu,
Yu-biao Gao,
Bao-jin Zhou,
Ruo Zhou,
Fu-ming Chen,
Fu-rong Li
Affiliations
Hao-jie Yan
Translational Medicine Collaborative Innovation Center, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), 518020, Shenzhen, China; Post-doctoral Scientific Research Station of Basic Medicine, Jinan University, 510632, Guangzhou, China; Guangdong Engineering Technology Research Center of Stem Cell and Cell Therapy, Shenzhen Key Laboratory of Stem Cell Research and Clinical Transformation, Shenzhen Immune Cell Therapy Public Service Platform, 518020, Shenzhen, China
Sheng-cheng Lin
Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital and Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 518172, Shenzhen, China
Shao-hang Xu
Deepxomics Co., Ltd, 518112, Shenzhen, China
Yu-biao Gao
Translational Medicine Collaborative Innovation Center, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), 518020, Shenzhen, China; Guangdong Engineering Technology Research Center of Stem Cell and Cell Therapy, Shenzhen Key Laboratory of Stem Cell Research and Clinical Transformation, Shenzhen Immune Cell Therapy Public Service Platform, 518020, Shenzhen, China
Bao-jin Zhou
Experiment Center for Science and Technology, Shanghai University of Traditional Chinese Medicine, 201203, Shanghai, China
Ruo Zhou
Deepxomics Co., Ltd, 518112, Shenzhen, China
Fu-ming Chen
Translational Medicine Collaborative Innovation Center, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), 518020, Shenzhen, China; Guangdong Engineering Technology Research Center of Stem Cell and Cell Therapy, Shenzhen Key Laboratory of Stem Cell Research and Clinical Transformation, Shenzhen Immune Cell Therapy Public Service Platform, 518020, Shenzhen, China
Fu-rong Li
Translational Medicine Collaborative Innovation Center, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), 518020, Shenzhen, China; Guangdong Engineering Technology Research Center of Stem Cell and Cell Therapy, Shenzhen Key Laboratory of Stem Cell Research and Clinical Transformation, Shenzhen Immune Cell Therapy Public Service Platform, 518020, Shenzhen, China; Institute of Health Medicine, Southern University of Science and Technology, 518055, Shenzhen, China; Corresponding author. Translational Medicine Collaborative Innovation Center, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), 518020, Shenzhen, China.
Objectives: Lung adenocarcinomas have different prognoses depending on their histological growth patterns. Micropapillary growth within lung adenocarcinoma, particularly metastasis, is related to dismal prognostic outcome. Metastasis accounts for a major factor leading to mortality among lung cancer patients. Understanding the mechanisms underlying early stage metastasis can help develop novel treatments for improving patient survival. Methods: Here, quantitative mass spectrometry was conducted for comparing protein expression profiles among various histological subtypes, including adenocarcinoma in situ, minimally invasive adenocarcinoma, and invasive adenocarcinoma (including acinar and micropapillary [MIP] types). To determine the mechanism of MIP-associated metastasis, we identified a protein that was highly expressed in MIP. The expression of the selected highly expressed MIP protein was verified via immunohistochemical (IHC) analysis and its function was validated by an in vitro migration assay. Results: Proteomic data revealed that low-density lipoprotein receptor-related protein–associated protein 1 (LRPAP1) was highly expressed in MIP group, which was confirmed by IHC. The co-expressed proteins in this study, PSMD1 and HSP90AB1, have been reported to be highly expressed in different cancers and play an essential role in metastasis. We observed that LRPAP1 promoted lung cancer progression, including metastasis, invasion and proliferation in vitro and in vivo. Conclusion: LRPAP1 is necessary for MIP-associated metastasis and is the candidate novel anti-metastasis therapeutic target.
