کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8707500 | 1586235 | 2017 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Differential roles of kallikrein-related peptidase 6 in malignant transformation and ÎNp63β-mediated epithelial-mesenchymal transition of oral squamous cell carcinoma
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کلمات کلیدی
DMEMOSCCΔNp63Dulbecco’s modified Eagle medium - Modified Eagle اصلاح شده DulbeccoMalignant transformation - تحول بدخیمEMT - تکنسین فوریتهای پزشکیreverse transcription - رونویسی معکوسOral cancer - سرطان دهانMetastasis - متاستاز prognosis - پیش شناخت بیماریOral squamous cell carcinoma (OSCC) - کارسینوم سلول سنگفرشی خوراکی (OSCC)oral squamous cell carcinoma - کارسینوم سلول سنگفرشی دهانیepithelial-to-mesenchymal transition - گذار اپیتلیال به مزانشیمالEpithelial-to-mesenchymal transition (EMT) - گذار اپیتلیال به مزانشیمی (EMT)protease-activated receptor - گیرنده پروتئاز فعال
موضوعات مرتبط
علوم پزشکی و سلامت
پزشکی و دندانپزشکی
دندانپزشکی، جراحی دهان و پزشکی
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چکیده انگلیسی
We previously reported that epithelial-to-mesenchymal transition (EMT) was mediated by ÎNp63β in oral squamous cell carcinoma (OSCC). In this study, DNA microarray analyses were performed using ÎNp63β-overexpressing OSCC cells to identify genes associated with ÎNp63β-mediated EMT. Thereby, we focused on kallikrein-related peptidase (KLK) 6, most up-regulated following ÎNp63β-overexpression, that activates protease-activated receptors (PARs). In RT-PCR analyses, ÎNp63 was positively associated with KLK6 and PAR2 and negatively with PAR1 in OSCC cells. By ÎNp63 knockdown, KLK6 and PAR2 expression was decreased and PAR1 was increased. Furthermore, KLK6 knockdown led to enhancing migration and invasion, and inhibiting proliferation, suggesting EMT-phenotypes. Although, in the KLK6 or PAR2 knockdown cells, phosphorylation of ERK was reduced, it was restored in the KLK6 knockdown OSCC cells treated with recombinant KLK6 proteins. Immunohistochemistry showed ÎNp63, KLK6, and PAR2 were more strongly expressed in the epithelial dysplasia and central region of OSCC than normal oral epithelium, whereas PAR1 expression was undetectable. Interestingly, at the invasive front of OSCC, ÎNp63, KLK6, and PAR2 were reduced, but PAR1 was elevated. In addition, the OSCC patients with decreasing KLK6 expression at the invasive front had more unfavourable prognosis. These results suggested differential roles of KLK6 in malignant transformation and EMT; high ÎNp63β expression up-regulates KLK6-PAR2 and down-regulates PAR1, inducing malignant transformation in oral epithelium with stimulating proliferation through ERK signal activation. Moreover, KLK6-PAR2 expression is down-regulated and PAR1 is up-regulated when ÎNp63β expression is decreased, leading to EMT with enhancing migration and invasion through ERK signal reduction at the invasive front.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Oral Oncology - Volume 75, December 2017, Pages 148-157
Journal: Oral Oncology - Volume 75, December 2017, Pages 148-157
نویسندگان
Naoki Kaneko, Shintaro Kawano, Kaori Yasuda, Yuma Hashiguchi, Taiki Sakamoto, Ryota Matsubara, Yuichi Goto, Teppei Jinno, Yasuyuki Maruse, Masahiko Morioka, Taichi Hattori, Shoichi Tanaka, Hideaki Tanaka, Tamotsu Kiyoshima, Seiji Nakamura,