Promotion of Tumor Cell Metastasis and Vasculogenic Mimicry by Way of Transcription Coactivation by Bcl-2 and Twist1: A Study of Hepatocellular Carcinoma

被引：146

作者：

Sun, Tao ^{[1
]}

Sun, Bao-cun ^{[1
,2
]}

Zhao, Xiu-lan ^{[1
]}

Zhao, Nan ^{[1
]}

Dong, Xue-yi ^{[1
]}

Che, Na ^{[1
]}

Yao, Zhi ^{[1
]}

Ma, Yue-mei ^{[1
]}

Gu, Qiang ^{[1
]}

Zong, Wen-kang ^{[1
]}

Liu, Zhi-yong ^{[2
]}

机构：

[1] Tianjin Med Univ, Dept Pathol, Tianjin 300070, Peoples R China

[2] Tianjin Med Univ, Dept Pathol, Tianjin Canc Hosp, Tianjin 300070, Peoples R China

来源：

HEPATOLOGY | 2011年 / 54卷 / 05期

基金：

中国国家自然科学基金;

关键词：

EPITHELIAL-MESENCHYMAL TRANSITION; STEM-LIKE CELLS; PROTEIN FAMILY; FUNCTIONAL-SIGNIFICANCE; FUTURE-PROSPECTS; IMMUNE-SYSTEM; BREAST-CANCER; EXPRESSION; HYPOXIA; MELANOMA;

D O I：

10.1002/hep.24543

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

The antiapoptotic protein Bcl-2 plays multiple roles in apoptosis, immunity, and autophagy. Its expression in tumors correlates with tumor grade and malignancy. The recapitulation of the normal developmental process of epithelial-mesenchymal transition (EMT) contributes to tumor cell plasticity. This process is also a characteristic of metastatic cells and vasculogenic mimicry. In the present study we report functional and structural interactions between Bcl-2 and the EMT-regulating transcription factor Twist1 and the relationship with metastasis and vascular mimicry. Bcl-2 and Twist1 are coexpressed under hypoxia conditions. The Bcl-2 can bind to Twist1 in vivo and in vitro. This interaction involves basic helix-loop-helix DNA binding domain within Twist1 and through two separate domains within Bcl-2 protein. Formation of the Bcl-2/Twist1 complex facilitates the nuclear transport of Twist1 and leads to transcriptional activation of wide ranges of genes that can increase the tumor cell plasticity, metastasis, and vasculogenic mimicry. Finally, nuclear expression of Bcl-2 and Twist1 is correlated with poor survival of these patients in a cohort of 97 cases of human hepatocellular carcinoma. Conclusion: The results describe a novel function of Bcl-2 in EMT induction, provide insight into tumor progression, and implicate the Bcl-2/Twist1 complex as a potential target for developing chemotherapeutics. (HEPATOLOGY 2011;54:1690-1706)

引用

页码：1690 / 1706

页数：17

共 34 条

[1] The paradoxical association between Bcl-2 expression and prognosis: Does the immune system make the difference? [J].

Becker, JC ;

Straten, PT ;

Andersen, MH .

CANCER RESEARCH, 2005, 65 (07) :2983-2983

[2] Opposite role of Bax and BCL-2 in the anti-tumoral responses of the immune system [J].

Bougras, G ;

Cartron, PF ;

Gautier, F ;

Martin, S ;

LeCabellec, M ;

Meflah, K ;

Gregoire, M ;

Vallette, FM .

BMC CANCER, 2004, 4 (1)

[3] BH3 mimetics antagonizing restricted prosurvival Bcl-2 proteins represent another class of selective immune modulatory drugs [J].

Carrington, Emma M. ;

Vikstrom, Ingela B. ;

Light, Amanda ;

Sutherland, Robyn M. ;

Londrigan, Sarah L. ;

Mason, Kylie D. ;

Huang, David C. S. ;

Lew, Andrew M. ;

Tarlinton, David M. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2010, 107 (24) :10967-10971

[4] Curcumin inhibits proliferation and migration by increasing the Bax to Bcl-2 ratio and decreasing NF-κBp65 expression in breast cancer MDA-MB-231 cells [J].

Chiu, Tsung-Lang ;

Su, Chin-Cheng .

INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE, 2009, 23 (04) :469-475

[5] The role of the Bcl-2 protein family in cancer [J].

Coultas, L ;

Strasser, A .

SEMINARS IN CANCER BIOLOGY, 2003, 13 (02) :115-123

[6] Expression and functional significance of VE-cadherin in aggressive human melanoma cells: Role in vasculogenic mimicry [J].

Hendrix, MJC ;

Seftor, EA ;

Meltzer, PS ;

Gardner, LMG ;

Hess, AR ;

Kirschmann, DA ;

Schatteman, GC ;

Seftor, REB .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (14) :8018-8023

[7] Epithelial-mesenchymal transitions:: Twist in development and metastasis [J].

Kang, YB ;

Massagué, J .

CELL, 2004, 118 (03) :277-279

[8] Twist overexpression correlates with hepatocellular carcinoma metastasis through induction of epithelial-mesenchymal transition [J].

Lee, Terence K. ;

Poon, Ronnie T. P. ;

Yuen, Anthony P. ;

Ling, Ming Tat ;

Kwok, Wei Kei ;

Wang, Xiang Hong ;

Wong, Yong Chuan ;

Guan, Xin Yuan ;

Man, Kwan ;

Chau, King Lok ;

Fan, Sheung Tat .

CLINICAL CANCER RESEARCH, 2006, 12 (18) :5369-5376

[9] Hypoxia and breast cancer: prognostic and therapeutic implications [J].

Lundgren, K. ;

Holm, C. ;

Landberg, G. .

CELLULAR AND MOLECULAR LIFE SCIENCES, 2007, 64 (24) :3233-3247

[10] Twist expression promotes migration and invasion in hepatocellular carcinoma [J].

Matsuo, Noriyuki ;

Shiraha, Hidenori ;

Fujikawa, Tatsuya ;

Takaoka, Nobuyuki ;

Ueda, Naoki ;

Tanaka, Shigetomi ;

Nishina, Shinichi ;

Nakanishi, Yutaka ;

Uemura, Masayuki ;

Takaki, Akinobu ;

Nakamura, Shinichiro ;

Kobayashi, Yoshiyuki ;

Nouso, Kazuhiro ;

Yagi, Takahito ;

Yamamoto, Kazuhide .

BMC CANCER, 2009, 9

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