Myosin light chain kinase is a potential target for hypopharyngeal cancer treatment

被引:5
作者
Cao, Feng [1 ,2 ]
Zhu, Le [3 ,4 ,5 ]
Zhang, Jing [3 ,4 ,5 ]
Pongkorpsakol, Pawin [6 ]
Kuo, Wei-Ting [7 ,8 ]
Turner, Jerrold R. [7 ,8 ]
Zhou, Qing [3 ,4 ,5 ]
Wang, Yuan [3 ,4 ,5 ]
Chen, Feihu [9 ]
Liu, Yehai [1 ]
Zuo, Li [3 ,4 ,5 ,7 ,8 ]
机构
[1] Anhui Med Univ, Dept Otorhinolaryngol Head & Neck Surg, Affiliated Hosp 1, Hefei 230032, Peoples R China
[2] Second Peoples Hosp Hefei, Dept Otorhinolaryngol Head & Neck Surg, Hefei 230001, Peoples R China
[3] Anhui Med Univ, Lab Mol Biol, Hefei 230032, Anhui, Peoples R China
[4] Anhui Med Univ, Dept Biochem, Hefei 230032, Anhui, Peoples R China
[5] Key Lab Gene Res Anhui Prov, Hefei 230032, Anhui, Peoples R China
[6] Mahidol Univ, Ramathibodi Hosp, Fac Med, Translat Med Grad Program, Bangkok, Thailand
[7] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA
[8] Harvard Med Sch, Boston, MA 02115 USA
[9] Anhui Med Univ, Coll Pharm, Hefei, Peoples R China
基金
中国国家自然科学基金;
关键词
Hypopharyngeal cancer; MLCK; ATRA; ATPR; TRANS-RETINOIC ACID; SQUAMOUS-CELL CARCINOMA; EXPRESSION; MIGRATION; MLCK; HEAD; NECK; PHOSPHORYLATION; PROLIFERATION; DIFFERENTIATION;
D O I
10.1016/j.biopha.2020.110665
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Hypopharyngeal cancer is squamous cell carcinoma (SCC) with the worst prognosis among the head and neck cancers. Overall, the 5-year survival rate remains poor although diagnostic imaging, radiation, chemotherapy, and surgical techniques have been improved. The mortality of patients with hypopharyngeal cancer is partly due to an increased likelihood of developing a second primary malignancy and metastasis. In this study, we found that MLCK expression, compared to healthy tissue, was up-regulated in hypopharyngeal tumor tissue. Of particular interest, a low 5-year survival rate was positively correlated with MLCK expression. We hypothesized that MLCK might be a target for hypopharyngeal cancer prognosis and treatment. In order to explore the function of MLCK in the development of cancer, we knockdown MLCK in hypopharyngeal cancer FaDu cells. The results showed that MLCK knockdown reduced the migration and invasion of FaDu cells. 4-amino-2-trifluoromethyl-phenyl retinate (ATPR) is the derivative of all-trans retinoic acid (ATRA), which was able to reduce both MLCK expression and activity in FaDu cells. ATPR induced FaDu cells apoptosis in a dose-dependent manner and also inhibited cell growth both in vivo and in vitro. Further experiments showed that overexpression of MLCK reduced ATPR induced-migration inhibition while increase of ATPR induced apoptosis, which suggested that MLCK was involved in ATPR's anti-cancer function. In conclusion, MLCK is a novel prognostic marker and therapeutic target for hypopharyngeal cancer. By targeting MLCK, ATPR exhibits its potential application in the treatment of this type of cancer.
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页数:11
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