title: HCRP1 is downregulated in non-small cell lung cancer and regulates proliferation, invasion, and drug resistance.
abstract: HCRP1 has been reported to have tumor suppressive function. However, its expression pattern and function in human non-small cell lung cancer (NSCLC) remain obscure. This study aims to explore clinical significance of HCRP1 in NSCLC. Immunohistochemical results showed high HCRP1 protein in normal bronchial epithelial tissue and downregulated HCRP1 expression in 47/98 lung cancer specimens. HCRP1 downregulation correlated with clinical stage (p = 0.0203), nodal status (p = 0.0168), and poor patient prognosis (log-rank, p = 0.0076). Univariate analysis showed that TNM stage (p < 0.0001) and HCRP1 (p = 0.0098) were significant prognostic factors; Cox regression model showed that TNM stage serves as an independent prognostic factor (p = 0.0011). We also found that HCRP1 was downregulated in lung cancer cells compared with normal HBE cells. HCRP1 plasmid transfection in H1299 cells inhibited proliferation, cell cycle progression, and invasion. HCRP1 depletion in A549 cells showed the opposite biological effects. In addition, we found that HCRP1 could inhibit MAPK and AKT signaling with downregulation of ERK and AKT phosphorylation, cyclin proteins, Bcl2 and MMP9, while HCRP1 depletion activated ERK and AKT signaling. The level of EGFR phosphorylation was also inhibited by HCRP1. In addition, we found that HCRP1 depletion confers multidrug resistance in H1299 cells. We employed paclitaxel and cisplatin in A549 cells with HCRP1 depletion. HCRP1 depletion decreased the effect of paclitaxel and cisplatin in A549 cells. Treatment with EGFR inhibitor AG1478 and AKT inhibitor LY249004 abolished the effect of HCRP1 depletion on drug resistance. In conclusion, the present study demonstrate that HCRP1 is downregulated in NSCLC and regulates proliferation, invasion, and drug resistance through modulation of EGFR signaling.
authors.affiliation: Department of Cardiovascular Thoracic Surgery, The First Affiliated Hospital of Jinzhou Medical University, Jingzhou City, People's Republic of China.
authors.forename: Yaming
authors.initials: Y
authors.lastname: Du
authors.affiliation: Department of Cardiovascular Thoracic Surgery, The First Affiliated Hospital of Jinzhou Medical University, Jingzhou City, People's Republic of China.
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of Tumor Center, The First Affiliated Hospital of Jinzhou Medical University, NO.2, Section 5 Rinmin Street, Guta District, Jingzhou City, 121001, Liaoning, People's Republic of China. sunhongzhily@sina.com.
authors.forename: Hongzhi
authors.initials: H
authors.lastname: Sun
authors.affiliation: Department of Pathology, Jinzhou Medical University, Jingzhou City, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Cardiovascular Thoracic Surgery, The First Affiliated Hospital of Jinzhou Medical University, Jingzhou City, People's Republic of China.
authors.forename: Xianping
authors.initials: X
authors.lastname: Lang
authors.affiliation: Department of Cardiovascular Thoracic Surgery, The First Affiliated Hospital of Jinzhou Medical University, Jingzhou City, People's Republic of China.
authors.forename: Zhongbin
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Cardiovascular Thoracic Surgery, The First Affiliated Hospital of Jinzhou Medical University, Jingzhou City, People's Republic of China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Zang
authors.affiliation: Department of Cardiovascular Thoracic Surgery, The First Affiliated Hospital of Jinzhou Medical University, Jingzhou City, People's Republic of China.
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Cardiovascular Thoracic Surgery, The First Affiliated Hospital of Jinzhou Medical University, Jingzhou City, People's Republic of China.
authors.forename: Junjun
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Cardiovascular Thoracic Surgery, The First Affiliated Hospital of Jinzhou Medical University, Jingzhou City, People's Republic of China.
authors.forename: Daohan
authors.initials: D
authors.lastname: Sun
keywords: EGFR; HCRP1; Non-small cell lung cancer; Proliferation; Resistance