Along with its favorable prognostic role, CLCA2 inhibits growth and metastasis of nasopharyngeal carcinoma cells via inhibition of FAK/ERK signaling.
Along with its favorable prognostic role, CLCA2 inhibits growth and metastasis of nasopharyngeal carcinoma cells via inhibition of FAK/ERK signaling.
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除了具有良好的预后作用外，CLCA2还通过抑制FAK/ERK信号传导来抑制鼻咽癌细胞的生长和转移
DOI：
10.1186/s13046-018-0692-8
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发表时间：
2018-02-20
期刊：
影响因子：
--
通讯作者：
Qian CN
中科院分区：
文献类型：
--
作者：
Qiang YY;Li CZ;Sun R;Zheng LS;Peng LX;Yang JP;Meng DF;Lang YH;Mei Y;Xie P;Xu L;Cao Y;Wei WW;Cao L;Hu H;Yang Q;Luo DH;Liang YY;Huang BJ;Qian CN
背景CLCA 2是一种抑癌基因，在乳腺癌中表达异常。然而，其在鼻咽癌生长和转移中的作用却鲜有报道。方法采用实时荧光定量PCR（real-time PCR，RT-PCR）、免疫印迹（Western blot）和免疫组化（IHC）方法检测CLCA 2在人鼻咽癌细胞系和组织中的表达。在5- 8 F、S18、S26和SUNE-1细胞中检测CLCA 2在鼻咽癌细胞系增殖、迁移和侵袭中的生物学作用。分别采用MTS法、集落形成法和transwell法检测细胞活力、迁移和侵袭能力。结果CLCA 2过表达可明显抑制鼻咽癌细胞的增殖、迁移和侵袭能力，抑制鼻咽癌细胞的增殖和侵袭能力。相反，CLCA 2的敲低引起相反的效果。CLCA 2过表达抑制异种移植肿瘤生长和肺、腘淋巴结（LN）转移。CLCA 2通过抑制上皮-间充质转化（EMT）和阻断FAK/ERK 1/2信号通路抑制鼻咽癌细胞的转移。143例NPC标本的免疫组化染色显示，CLCA 2表达是患者总生存率和无远处转移生存率的独立、有利的预后因素。此外，抑制FAK和ERK 1/2逆转了CLCA 2沉默诱导的肿瘤细胞迁移。结论CLCA 2通过抑制FAK/ERK信号通路抑制鼻咽癌细胞的增殖、迁移、侵袭和上皮间质转化。
BackgroundCLCA2 was reported as a tumor suppressor and disregulated in breast cancer. However, its function in tumor growth and metastasis in NPC has rarely been reported. In this study, we investigated the functional and molecular mechanisms by which CLCA2 influences NPC.MethodsCLCA2 expression in human NPC cell lines and tissues was examined via real-time PCR (RT-PCR), Western blot and IHC. The biological roles of CLCA2 in proliferative, migration and invasion of NPC cell lines was evaluated in 5-8F, S18, S26 and SUNE-1 cells. Cell viability, migration and invasion were assessed in vitro by MTS, colony formation and transwell assay, respectively. CLCA2 in growth and metastasis of NPC were evaluated in vivo through NPC xenograft tumor growth, lung metastatic mice model and popliteal lymph node (LN) metastasis model.ResultsOverexpression of CLCA2 significantly decreased proliferation, migration and invasion of NPC cells. In contrast, knockdown of CLCA2 elicited the opposite effects. CLCA2 overexpression suppressed xenograft tumor growth and lung, popliteal lymph node (LN) metastasis in vivo. CLCA2 inhibited tumor metastasis through suppressing epithelial-Mesenchymal transition (EMT) and in-activating FAK/ERK1/2 signaling pathway in NPC cells. Immunohistochemical staining of 143 NPC samples revealed that CLCA2 expression was an independent, favorable prognostic factor for overall survival and distant metastasis-free survival of patients. In addition, inhibition of FAK and ERK1/2 reversed CLCA2 silencing-induced tumor cell migration. Furthermore, inhibitors against chloride channels suppressed NPC cellular migration which could have been enhanced by the presence of CLCA2.ConclusionCLCA2 suppress NPC proliferation, migration, invasion and epithelial-mesenchymal transition through inhibiting FAK/ERK signaling.
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影响因子：
10.3
作者：
Bart, G.;Hamalainen, L.;Tammi, R. H.
通讯作者：
Tammi, R. H.
影响因子：
4.8
作者：
Elble, Randolph C.;Walia, Vijay;Pauli, Bendicht U.
通讯作者：
Pauli, Bendicht U.
DOI：
10.1158/1078-0432.ccr-17-1561
发表时间：
2017-12-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Godse NR;Khan N;Yochum ZA;Gomez-Casal R;Kemp C;Shiwarski DJ;Seethala RS;Kulich S;Seshadri M;Burns TF;Duvvuri U
通讯作者：
Duvvuri U
丝甘氨酸是鼻咽癌促进转移的治疗诊断靶点
影响因子：
11.2
作者：
Li, Xin-Jian;Ong, Choon Kiat;Qian, Chao-Nan
通讯作者：
Qian, Chao-Nan
DOI：
10.1073/pnas.1217072110
发表时间：
2013-03-12
影响因子：
11.1
作者：
Britschgi, Adrian;Bill, Anke;Bentires-Alj, Mohamed
通讯作者：
Bentires-Alj, Mohamed