A potential prognostic marker and therapeutic target: SPOCK1 promotes the proliferation, metastasis, and apoptosis of pancreatic ductal adenocarcinoma cells. Issue 1 (3rd September 2019)

• Record Type: Journal Article
• Authors: Li, Jia; Ke, Jing; Fang, Jun; Chen, Jin‐Peng
• Is Part Of: Journal of cellular biochemistry. Volume 121:Issue 1(2020)
• Page Start: 743
• Page End: 754
• Publication Date: 2019-09-03
• Subjects: pancreatic ductal adenocarcinoma -- prognosis -- SPOCK1 -- tumor progression; Cytochemistry -- Periodicals; 572
• DOI: 10.1002/jcb.29320
• Languages: English
• ISSNs: 0730-2312

Abstract

Abstract: Pancreatic ductal adenocarcinoma (PDAC), a common malignancy originated from the digestive system worldwide, has a poor clinical outcome. SPOCK1 is a widely investigated member of the Ca 2+ ‐binding proteoglycan family and functions as an essential driver in several cancers. However, the complex regulatory role of SPOCK1 in PDAC is unclear. Bioinformatics analysis predicted an interrelationship between increased SPOCK1 expression and the clinical characteristics of patients with PDAC. The SPOCK1 expression levels in fresh tissue samples were confirmed, and SPOCK1 expression was then knocked down by lentivirus‐mediated short hairpin RNA. Cell proliferation, metastasis, and apoptosis were detected through Cell Counting Kit‐8, colony formation assays, invasion and migration assays, flow cytometric analysis, quantitative real‐time polymerase chain reaction, and Western blot experiment. On the basis of the Cancer Genome Atlas database, we found a significantly higher level of SPOCK1 in PDAC than in adjacent nontumor tissues. Patients with PDAC with high SPOCK1 expression exhibited shorter overall survival time, as well as disease‐free survival time. The knockdown of SPOCK1 significantly decreased the proliferation and metastasis of PCNA‐1 and MIA PaCa‐2 cells. Moreover, the knockdown of SPOCK1 led to cell cycle arrest in G0/G1 phase and increased the proportion of apoptotic PDAC cells by regulating members of the caspase and Bcl‐2 families. Our data proved that SPOCK1 is a critical regulator of tumor proliferation and metastasis in PDAC cells. Therefore, SPOCK1 might be a potential prognostic and therapeutic target molecule in PDAC. Abstract : SPOCK1 over expression in PDAC patients was associated with tumor size, lymph node metastasis and worse overall survival. SPOCK1 might serve as an oncogene in PDAC pathogenesis by inactivating the PI3K/Akt signaling pathway.