PSPH Mediates the Metastasis and Proliferation of Non-small Cell Lung Cancer through MAPK Signaling Pathways

被引:32
作者
Liao, Li [1 ]
Ge, Mengxi [1 ]
Zhan, Qiong [1 ]
Huang, Ruofan [1 ]
Ji, Xiaoyu [1 ]
Liang, Xiaohua [1 ]
Zhou, Xinli [1 ]
机构
[1] Fudan Univ, Huashan Hosp, Dept Oncol, 12 Middle Urumqi Rd, Shanghai 200040, Peoples R China
关键词
PSPH; NSCLC; metastasis; proliferation; MAPK; SERINE BIOSYNTHESIS PATHWAY; L-3-PHOSPHOSERINE PHOSPHATASE; PHOSPHOSERINE PHOSPHATASE; BRAIN METASTASES; DEFICIENCY; ACTIVATION; EXPRESSION; CARCINOMA; DIAGNOSIS;
D O I
10.7150/ijbs.29203
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Growing evidence indicates that phosphoserine phosphatase (PSPH) is up-regulated and correlates with prognosis in multiple types of cancer. However, little is known about the roles of PSPH in NSCLC. Thus, the aim of the present study was to demonstrate the expression of PSPH in human NSCLC and reveal its biological functions and the underlying mechanisms. qRT-PCR, western blot and immunohistochemistry were used to assess the expression of NSCLC patient specimens and NSCLC cell lines. The functions of PSPH in migration and invasion were determined using trans-well and wound-healing assays. Cell proliferation capacity was performed by cell counting kit-8 (CCK-8), colony formation assays and cell cycle analysis. We demonstrated that PSPH was overexpressed in NSCLC specimens compared with the adjacent non-tumorous specimens, and high expression of PSPH was associated with clinical stage, metastasis and gender in NSCLC. Decreased expression of PSPH inhibited NSCLC cells migration, invasion and proliferation. Most importantly, further experiments demonstrated that PSPH might regulate NSCLC progress through MAPK signaling pathways. Lastly, immunohistochemistry (IHC) revealed that the PSPH expression level was positively correlated with the clinical stage in NSCLC patients. These results suggest that PSPH may act as a putative oncogene and a potential therapeutic target in NSCLC.
引用
收藏
页码:183 / 194
页数:12
相关论文
共 26 条
[1]   Analysis of PSPHL as a candidate gene influencing the racial disparity in endometrial cancer [J].
Allard, Jay E. ;
Chandramouli, Gadisetti V. R. ;
Stagliano, Katherine ;
Hood, Brian L. ;
Litzi, Tracy ;
Shoji, Yutaka ;
Boyd, Jeff ;
Berchuck, Andrew ;
Conrads, Thomas P. ;
Maxwell, G. Larry ;
Risinger, John I. .
FRONTIERS IN ONCOLOGY, 2012, 2 :1-15
[2]   L-3-Phosphoserine phosphatase (PSPH) regulates cutaneous squamous cell carcinoma proliferation independent of L-serine biosynthesis [J].
Bachelor, Michael A. ;
Lu, Yan ;
Owens, David M. .
JOURNAL OF DERMATOLOGICAL SCIENCE, 2011, 63 (03) :164-172
[3]   Race-associated biological differences among Luminal A breast tumors [J].
D'Arcy, Monica ;
Fleming, Jodie ;
Robinson, Whitney R. ;
Kirk, Erin L. ;
Perou, Charles M. ;
Troester, Melissa A. .
BREAST CANCER RESEARCH AND TREATMENT, 2015, 152 (02) :437-448
[4]   Prospects for population screening and diagnosis of lung cancer [J].
Field, John K. ;
Oudkerk, Matthijs ;
Pedersen, Jesper Holst ;
Duffy, Stephen W. .
LANCET, 2013, 382 (9893) :732-741
[5]   Cancer metastasis:: Building a framework [J].
Gupta, Gaorav P. ;
Massague, Joan .
CELL, 2006, 127 (04) :679-695
[6]   Eleven Candidate Susceptibility Genes for Common Familial Colorectal Cancer [J].
Gylfe, Alexandra E. ;
Katainen, Riku ;
Kondelin, Johanna ;
Tanskanen, Tomas ;
Cajuso, Tatiana ;
Hanninen, Ulrika ;
Taipale, Jussi ;
Taipale, Minna ;
Renkonen-Sinisalo, Laura ;
Jarvinen, Heikki ;
Mecklin, Jukka-Pekka ;
Kilpivaara, Outi ;
Pitkanen, Esa ;
Vahteristo, Pia ;
Tuupanen, Sari ;
Karhu, Auli ;
Aaltonen, Lauri A. .
PLOS GENETICS, 2013, 9 (10)
[7]   Factors Associated With the Development of Brain Metastases Analysis of 975 Patients With Early Stage Nonsmall Cell Lung Cancer [J].
Hubbs, Jessica L. ;
Boyd, Jessamy A. ;
Hollis, Donna ;
Chino, Junzo P. ;
Saynak, Mert ;
Kelsey, Chris R. .
CANCER, 2010, 116 (21) :5038-5046
[8]   Inhibition of phosphoserine phosphatase enhances the anticancer efficacy of 5-fluorouracil in colorectal cancer [J].
Li, Xin ;
Xun, Zhe ;
Yang, Yong .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2016, 477 (04) :633-639
[9]   Enhanced serine production by bone metastatic breast cancer cells stimulates osteoclastogenesis [J].
Pollari, Sirkku ;
Kakonen, Sanna-Maria ;
Edgren, Henrik ;
Wolf, Maija ;
Kohonen, Pekka ;
Sara, Henri ;
Guise, Theresa ;
Nees, Matthias ;
Kallioniemi, Olli .
BREAST CANCER RESEARCH AND TREATMENT, 2011, 125 (02) :421-430
[10]   Metastatic sites and survival in lung cancer [J].
Riihimaeki, M. ;
Hemminki, A. ;
Fallah, M. ;
Thomsen, H. ;
Sundquist, K. ;
Sundquist, J. ;
Hemminki, K. .
LUNG CANCER, 2014, 86 (01) :78-84