Sphingosine kinase 1 plays a role in the upregulation of CD44 expression through extracellular signal-regulated kinase signaling in human colon cancer cells

被引：24

作者：

Kawahara, Satomi ^{[1
]}

Otsuji, Yoko ^{[1
]}

Nakamura, Mitsuhiro ^{[2
]}

Murakami, Masashi ^{[4
]}

Murate, Takashi ^{[5
]}

Matsunaga, Toshiyuki ^{[1
]}

Kanoh, Hiroyuki ^{[3
]}

Seishima, Mariko ^{[3
]}

Banno, Yoshiko ^{[3
]}

Hara, Akira ^{[1
]}

机构：

[1] Gifu Pharmaceut Univ, Dept Biochem, Gifu, Japan

[2] Gifu Pharmaceut Univ, Dept Pharm Practice & Sci, Gifu, Japan

[3] Gifu Univ, Grad Sch Med, Dept Dermatol, Gifu 5011194, Japan

[4] Natl Ctr Geriatr & Gerontol, Res Inst, Dept Oral Dis Res, Obu, Japan

[5] Nagoya Univ, Sch Hlth Sci, Dept Med Technol, Nagoya, Aichi 4648601, Japan

来源：

ANTI-CANCER DRUGS | 2013年 / 24卷 / 05期

关键词：

CD44; colon cancer cell; extracellular signal-regulated kinase signaling; oxaliplatin resistance; sphingosine kinase 1; DOWN-REGULATION; SPHINGOSINE-1-PHOSPHATE; APOPTOSIS; MIGRATION; RESISTANCE; LEUKEMIA; GROWTH; 1-PHOSPHATE; SENSITIVITY; ACTIVATION;

D O I：

10.1097/CAD.0b013e32835f705f

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

Our previous study has shown that the activity and expression of sphingosine kinase (SPHK) regulated the sensitivity of human colon cancer cells to the chemotherapeutic oxaliplatin (L-OHP). In addition, the cancer stem cell marker CD44 increases cell resistance to anticancer drugs. Here, we use colon cancer cell lines to examine the relationship between SPHK1 activity and CD44 expression. CD44 expression was measured by western blotting and quantitative PCR in two human colon cancer cell lines: L-OHP-resistant RKO and L-OHP-sensitive HCT116. The regulation of CD44 by SPHK1 was examined by either blocking or overexpressing SPHK1 and by using an L-OHP-resistant HCT116 clone (HCT116-R). The levels of SPHK1, CD44, phosphorylated-Akt, and phosphorylated-extracellular signal-regulated kinase (ERK) were much higher in the RKO cells than in the HCT116 cells. The treatment of RKO cells with the SPHK inhibitor or SPHK1 silencing by RNA interference suppressed CD44 protein expression. SPHK1 and CD44 levels were much higher in HCT116-R cells compared with the parental HCT116 cells. Transfection of HCT116 cells with SPHK1 cDNA enhanced the expression of both CD44 and phosphorylated-ERK. The increase in the CD44 protein level was abolished by the inhibition of ERK phosphorylation. Treatment of RKO cells with the sphingosine-1-phosphate (S1P)(2) receptor antagonist suppressed ERK phosphorylation and the expression of CD44 mRNA and protein. Exogenous stimulation with S1P increased ERK phosphorylation and CD44 protein expression in HCT116 cells, but treatment with an MEK inhibitor and S1P(2) receptor antagonist blocked this effect. These findings indicate that SPHK1 and its product, S1P, contribute toward the regulation of CD44 protein expression through the ERK signaling pathway through S1P(2) in human colon cancer cells. Anti-Cancer Drugs 24:473-483 (C) 2013 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins. Anti-Cancer Drugs 2013, 24:473-483

引用

页码：473 / 483

页数：11

共 44 条

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High expression of sphingosine kinase 1 and S1P receptors in chemotherapy-resistant prostate cancer PC3 cells and their camptothecin-induced up-regulation [J].