Artemin Stimulates Radio- and Chemo-resistance by Promoting TWIST1-BCL-2-dependent Cancer Stem Cell-like Behavior in Mammary Carcinoma Cells

被引:43
作者
Banerjee, Arindam [3 ]
Qian, PengXu [1 ,2 ]
Wu, Zheng-Sheng [1 ,2 ,4 ,5 ]
Ren, Xiaoge [3 ]
Steiner, Michael [3 ]
Bougen, Nicola M. [6 ,7 ]
Liu, Suling [1 ,2 ]
Liu, Dong-Xu [3 ]
Zhu, Tao [1 ,2 ]
Lobie, Peter E. [3 ,6 ,7 ]
机构
[1] Univ Sci & Technol China, Hefei Natl Lab Phys Sci Microscale, Hefei 230027, Anhui, Peoples R China
[2] Univ Sci & Technol China, Sch Life Sci, Hefei 230027, Anhui, Peoples R China
[3] Univ Auckland, Liggins Inst, Auckland 1023, New Zealand
[4] Anhui Med Univ, Dept Pathol, Hefei, Anhui, Peoples R China
[5] Fudan Univ, Shanghai Med Coll, Dept Pathol, Shanghai 200433, Peoples R China
[6] Natl Univ Singapore, Canc Sci Inst Singapore, Singapore 117599, Singapore
[7] Natl Univ Singapore, Dept Pharmacol, Singapore 117599, Singapore
基金
中国国家自然科学基金;
关键词
EPITHELIAL-MESENCHYMAL TRANSITION; BREAST-CANCER; GENE-EXPRESSION; ALDEHYDE DEHYDROGENASE; THERAPEUTIC TARGET; ESTROGEN-RECEPTOR; UP-REGULATION; GDNF FAMILY; CLAUDIN-LOW; BCL-2;
D O I
10.1074/jbc.M112.365163
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Artemin (ARTN) has been reported to promote a TWIST1-dependent epithelial to mesenchymal transition of estrogen receptor negative mammary carcinoma (ER-MC) cells associated with metastasis and poor survival outcome. We therefore examined a potential role of ARTN in the promotion of the cancer stem cell (CSC)-like phenotype in mammary carcinoma cells. Acquired resistance of ER-MC cells to either ionizing radiation (IR) or paclitaxel was accompanied by increased ARTN expression. Small interfering RNA (siRNA)-mediated depletion of ARTN in either IR- or paclitaxel-resistant ER-MC cells restored cell sensitivity to IR or paclitaxel. Expression of ARTN was enriched in ER-MC cells grown in mammospheric compared with monolayer culture and was also enriched along with BMI1, TWIST1, and DVL1 in mammospheric and ALDH1+ populations. ARTN promoted mammospheric growth and self-renewal of ER-MC cells and increased the ALDH1+ population, whereas siRNA-mediated depletion of ARTN diminished these CSC-like cell behaviors. Furthermore, increased ARTN expression was significantly correlated with ALDH1 expression in a cohort of ER-MC patients. Forced expression of ARTN also dramatically enhanced tumor initiating capacity of ER-MC cells in xenograft models at low inoculum. ARTN promotion of the CSC-like cell phenotype was mediated by TWIST1 regulation of BCL-2 expression. ARTN also enhanced mammosphere formation and the ALDH1 + population in estrogen receptor-positive mammary carcinoma (ER + MC) cells. Increased expression of ARTN and the functional consequences thereof may be one common adaptive mechanism used by mammary carcinoma cells to promote cell survival and renewal in hostile tumor microenvironments.
引用
收藏
页码:42502 / 42515
页数:14
相关论文
共 63 条
[1]   The GDNF family: Signalling, biological functions and therapeutic value [J].
Airaksinen, MS ;
Saarma, M .
NATURE REVIEWS NEUROSCIENCE, 2002, 3 (05) :383-394
[2]   TWISTing an embryonic transcription factor into an oncoprotein [J].
Ansieau, S. ;
Morel, A-P ;
Hinkal, G. ;
Bastid, J. ;
Puisieux, A. .
ONCOGENE, 2010, 29 (22) :3173-3184
[3]   Crosstalk between the estrogen receptor and the HER tyrosine kinase receptor family: Molecular mechanism and clinical implications for endocrine therapy resistance [J].
Arpino, Grazia ;
Wiechmann, Lisa ;
Osborne, C. Kent ;
Schiff, Rachel .
ENDOCRINE REVIEWS, 2008, 29 (02) :217-233
[4]   GFRα3 is an orphan member of the GDNF/neurturin/persephin receptor family [J].
Baloh, RH ;
Gorodinsky, A ;
Golden, JP ;
Tansey, MG ;
Keck, CL ;
Popescu, NC ;
Johnson, EM ;
Milbrandt, J .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (10) :5801-5806
[5]   ARTEMIN synergizes with TWIST1 to promote metastasis and poor survival outcome in patients with ER negative mammary carcinoma [J].
Banerjee, Arindam ;
Wu, Zheng-Sheng ;
Qian, PengXu ;
Kang, Jian ;
Pandey, Vijay ;
Liu, Dong-Xu ;
Zhu, Tao ;
Lobie, Peter E. .
BREAST CANCER RESEARCH, 2011, 13 (06)
[6]   Exploring the role of cancer stem cells in radioresistance [J].
Baumann, Michael ;
Krause, Mechthild ;
Hill, Richard .
NATURE REVIEWS CANCER, 2008, 8 (07) :545-554
[7]   GDNF family receptor complexes are emerging drug targets [J].
Bespalov, Maxim M. ;
Saarma, Mart .
TRENDS IN PHARMACOLOGICAL SCIENCES, 2007, 28 (02) :68-74
[8]   Heparan sulfate proteoglycan syndecan-3 is a novel receptor for GDNF, neurturin, and artemin [J].
Bespalov, Maxim M. ;
Sidorova, Yulia A. ;
Tumova, Sarka ;
Ahonen-Bishopp, Anni ;
Magalhaes, Ana Cathia ;
Kulesskiy, Evgeny ;
Paveliev, Mikhail ;
Rivera, Claudio ;
Rauvala, Heikki ;
Saarma, Mart .
JOURNAL OF CELL BIOLOGY, 2011, 192 (01) :153-169
[9]   Neurotrophic factor therapy for Parkinson's disease [J].
Bjorklund, Anders ;
Cenci, M. Angela .
RECENT ADVANCES IN PARKINSONS DISEASE: TRANSLATIONAL AND CLINICAL RESEARCH, 2010, 184 :237-264
[10]   The Ret receptor tyrosine kinase pathway functionally interacts with the ERα pathway in breast cancer [J].
Boulay, Anne ;
Breuleux, Madlaina ;
Stephan, Christine ;
Fux, Caroline ;
Brisken, Cathrin ;
Fiche, Maryse ;
Wartmann, Markus ;
Stumm, Michael ;
Lane, Heidi A. ;
Hynes, Nancy E. .
CANCER RESEARCH, 2008, 68 (10) :3743-3751