Abstract
Serine-arginine protein kinase 1 (SRPK1) phosphorylates proteins involved in the regulation of several mRNA processing pathways including alternative splicing. SRPK1 has been reported to be over-expressed in multiple cancers including prostate, breast, lung and glioma. Several studies further identified that inhibition of SRPK1 showed tumor-suppressive effects, thus raising SRPK1 as a novel candidate chemotherapy target. Interestingly, SRPK1 plays tumor suppressing role in mouse embryonic fibroblasts, on that SRPK1-silencing induces cell transformation. Therefore, the effect of SRPK1 seems heterogeneously in different cell types and tissues. The existence and role of SRPK1 in gastric cancer (GC) hasn’t been reported. Here we investigated the expression pattern of SRPK1 in GC by immunohistochemistry and found that it was up-regulated in tumor tissues, where its expression was correlated with tumor grade and prognosis. Further, we explored the signaling mechanism of SRPK1 in promoting GC progression, which revealed that both PP2A and DUSP6 phosphatases impaired the oncogenic effects of SRPK1. However, we didn’t find any direct interaction between SRPK1 with PP2A or DUSP6, indicating PP2A and DUSP6 function by regulating the downstream effectors of SRPK1. Our study not only revealed the clinical significance of SRPK1 in GC, but also provided new evidence for its signaling modulation which is invaluable for novel chemotherapy development.
Highlights
Gastric cancer (GC) is the one of the most common carcinoma and the second leading cause of cancer-related death worldwide [1, 2]
We investigated the expression pattern of Serine-arginine protein kinase 1 (SRPK1) in gastric cancer (GC) by immunohistochemistry and found that it was up-regulated in tumor tissues, where its expression was correlated with tumor grade and prognosis
Our study revealed the clinical significance of SRPK1 in GC, and provided new evidence for its signaling modulation which is invaluable for novel chemotherapy development
Summary
Gastric cancer (GC) is the one of the most common carcinoma and the second leading cause of cancer-related death worldwide [1, 2]. The only potentially curative treatment for GC is R0 surgical resection [3]. Most GC is diagnosed at an advanced stage [4], which is the major cause of unsatisfied overall survival (OS). More than 50% of patients will experience disease recurrence after surgery [5]. Despite advances in surgical intervention and chemotherapy, the overall prognosis of patients with advanced GC remains poor [6]. It is still an urgent need to identify novel biomarkers which correlate with GC tumorigenesis and progression
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