Carboxyl-terminal polypeptide fragment of MUC16 combing stathmin1 promotes gallbladder cancer cell migration and invasion

被引：10

作者：

Fan, Kun ^{[1
,2
,3
,4
]}

Zhang, Dexiang ^{[1
]}

Li, Min ^{[2
,3
,4
]}

Shen, Sheng ^{[2
,3
,4
]}

Wang, Jiwen ^{[2
,3
,4
]}

Ni, Xiaojian ^{[2
,3
,4
]}

Gong, Zijun ^{[2
,3
,4
]}

Zheng, Bohao ^{[2
,3
,4
]}

Gao, Zhihui ^{[2
,3
,4
]}

Ni, Xiaoling ^{[2
,3
,4
]}

Suo, Tao ^{[2
,3
,4
]}

Liu, Han ^{[2
,3
,4
]}

Liu, Houbao ^{[1
,2
,3
,4
]}

机构：

[1] Fudan Univ, Gen Surg Dept, Zhongshan Xuhui Hosp, Shanghai, Peoples R China

[2] Fudan Univ, Zhongshan Hosp, Dept Gen Surg, 180 Fenglin Rd, Shanghai, Peoples R China

[3] Fudan Univ, Zhongshan Hosp, Biliary Tract Dis Ctr, Shanghai, Peoples R China

[4] Fudan Univ, Biliary Tract Dis Inst, Shanghai, Peoples R China

来源：

MEDICAL ONCOLOGY | 2020年 / 37卷 / 12期

基金：

中国国家自然科学基金;

关键词：

Gallbladder cancer; Stathmin1; Microtubule; MUC16; C-terminal; Metastasis; PANCREATIC-CANCER; PHOSPHOPROTEIN FAMILY; MARKER;

D O I：

10.1007/s12032-020-01438-x

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

CA-125, coded by MUC16 gene, is responsible to many kinds of tumor metastasis. However, the related mechanism remains unclear. We have established a novel manner to reveal gallbladder cancer metastasis related to serum CA-125 levels through the C-terminal polypeptide of MUC16 gene production. MUC16 C-terminal polypeptide significantly promoted gallbladder cancer cell migration and invasion in vitro. Mass spectrum indicated that interaction of MUC16 C-terminal fragment with the C-terminal domain of stathmin1 inhibited the phosphorylation of stathmin1 to promote the combination with tubulin. Stathmin1 knockdown inhibited the migration and invasion of gallbladder cancer cells in vitro and lung metastasis in vivo induced by MUC16 C-terminal polypeptide. The high expression level of MUC16c consistent with stathmin1 was also confirmed in gallbladder cancer tissues. Our study revealed the underlying mechanism of gallbladder cancer metastasis related to CA-125 levels, which was beneficial for CA-125 in gallbladder cancer diagnose and therapy.

引用

页数：9

共 22 条

[1] CA 125: A potential tumor marker for gallbladder cancer [J].

Chaube, Amita ;

Tewari, Mallika ;

Singh, Usha ;

Shukla, H. S. .

JOURNAL OF SURGICAL ONCOLOGY, 2006, 93 (08) :665-669

[2] Stathmin 1 is a potential novel oncogene in melanoma [J].

Chen, J. ;

Abi-Daoud, M. ;

Wang, A. ;

Yang, X. ;

Zhang, X. ;

Feilotter, H. E. ;

Tron, V. A. .

ONCOGENE, 2013, 32 (10) :1330-1337

[3] The stathmin/tubulin interaction in vitro [J].

Curmi, PA ;

Andersen, SSL ;

Lachkar, S ;

Gavet, O ;

Karsenti, E ;

Knossow, M ;

Sobel, A .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (40) :25029-25036

[4]

Curmi PA, 1999, CELL STRUCT FUNCT, V24, P345

[5] Carboxyl-terminal domain of MUC16 imparts tumorigenic and metastatic functions through nuclear translocation of JAK2 to pancreatic cancer cells [J].

Das, Srustidhar ;

Rachagani, Satyanarayana ;

Torres-Gonzalez, Maria P. ;

Lakshmanan, Imayavaramban ;

Majhi, Prabin D. ;

Smith, Lynette M. ;

Wagner, Kay-Uwe ;

Batra, Surinder K. .

ONCOTARGET, 2015, 6 (08) :5772-5787

[6] MUC16 C-terminal binding with ALDOC disrupts the ability of ALDOC to sense glucose and promotes gallbladder carcinoma growth [J].

Fan, Kun ;

Wang, Jiwen ;

Sun, Wentao ;

Shen, Sheng ;

Ni, Xiaojian ;

Gong, Zijun ;

Zheng, Bohao ;

Gao, Zhihui ;

Ni, Xiaoling ;

Suo, Tao ;

Liu, Houbao ;

Liu, Han .

EXPERIMENTAL CELL RESEARCH, 2020, 394 (01)

[7] MUC16 C terminal-induced secretion of tumor-derived IL-6 contributes to tumor-associated Treg enrichment in pancreatic cancer [J].

Fan, Kun ;

Yang, Chao ;

Fan, Zhiyao ;

Huang, Qiuyi ;

Zhang, Yiyin ;

Cheng, He ;

Jin, Kaizhou ;

Lu, Yu ;

Wang, Zhengshi ;

Luo, Guopei ;

Yu, Xianjun ;

Liu, Chen .

CANCER LETTERS, 2018, 418 :167-175

[8] MUC16 (CA125): tumor biomarker to cancer therapy, a work in progress [J].

Felder, Mildred ;

Kapur, Arvinder ;

Gonzalez-Bosquet, Jesus ;

Horibata, Sachi ;

Heintz, Joseph ;

Albrecht, Ralph ;

Fass, Lucas ;

Kaur, Justanjyot ;

Hu, Kevin ;

Shojaei, Hadi ;

Whelan, Rebecca J. ;

Patankar, Manish S. .

MOLECULAR CANCER, 2014, 13

[9]

Gavet O, 1998, J CELL SCI, V111, P3333

[10] Gallbladder cancer: epidemiology and outcome [J].

Hundal, Rajveer ;

Shaffer, Eldon A. .

CLINICAL EPIDEMIOLOGY, 2014, 6 :99-109

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