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Lysophosphatidic acid upregulates calreticulin expression
in PC‐3 human prostate cancer cells
Author(s) -
Lu KuanYing,
Lin KuanHung,
Lin Chu cheng,
Lin YuehChien,
Yang YaJan,
Chen Weimin,
Hsia HsinYi,
Lee Hsinyu
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.974.2
Subject(s) - lysophosphatidic acid , gene knockdown , prostate cancer , cancer research , calreticulin , cancer cell , cancer , endoplasmic reticulum , chemistry , cell growth , biology , endocrinology , medicine , microbiology and biotechnology , apoptosis , receptor , biochemistry
Prostate cancer is one of the most commonly diagnosed cancers in males, and PC‐3 is a popular cell model for investigating late stage prostate cancer. Lysophosphatidic acid (LPA) is a low molecular weight lipid demonstrated to stimulate cell migration, invasion and proliferation in prostate cancer cells. In our previous study, calreticulin (CRT), a multifunctional Ca 2+ ‐binding chaperon, has been shown to associate with poor prognosis in gastric cancer and bladder cancer. However, the roles of CRT in prostate cancer remain elusive. It has been demonstrated that LPA evoked Ca 2+ mobilization from the lumen of the endoplasmic reticulum (ER) via phospholipase C (PLC) pathway. On the other hand, depletion of Ca 2+ from ER activated CRT promoter activity in NIH/3T3 cells. Based on these evidences, we hypothesized that LPA may regulate CRT expression. By using RT‐qPCR and Western Blotting, we found that CRT expression is up‐regulated both in mRNA and protein level after LPA treatment. Pharmacological blockade of LPA 1/3 by Ki16425 inhibitsthe enhancement effect of LPA on CRT. In addition, CRT expression is lower in LPA 1 and LPA 3 stable knockdown PC‐3 cells. Furthermore, activation of LPA 3 by OMPT enhances CRT expression. On the contrary, activation of LPA 2 by MDP and GRI977143 impaired CRT expression. Furthermore, knockdown of CRT resulted in decreased cell adherent ability and decreased expression of vascular endothelial growth factor‐A (VEGF‐A). Taken together, these results suggested that,LPA 1/3 and LPA 2 inversely regulate CRT expression and subsequently regulate cell adhesion and VEGF‐A expression in PC‐3 cells.