Crucial role of HMGA1 in the self-renewal and drug resistance of ovarian cancer stem cells View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2016-08-26

AUTHORS

Dae Kyoung Kim, Eun Jin Seo, Eun J Choi, Su In Lee, Yang Woo Kwon, Il Ho Jang, Seung-Chul Kim, Ki-Hyung Kim, Dong-Soo Suh, Kim Seong-Jang, Sang Chul Lee, Jae Ho Kim

ABSTRACT

Cancer stem cells are a subpopulation of cancer cells characterized by self-renewal ability, tumorigenesis and drug resistance. The aim of this study was to investigate the role of HMGA1, a chromatin remodeling factor abundantly expressed in many different cancers, in the regulation of cancer stem cells in ovarian cancer. Spheroid-forming cancer stem cells were isolated from A2780, SKOV3 and PA1 ovarian cancer cells by three-dimensional spheroid culture. Elevated expression of HMGA1 was observed in spheroid cells along with increased expression of stemness-related genes, such as SOX2, KLF4, ALDH, ABCB1 and ABCG2. Furthermore, spheroid A2780 cells, compared with adherent cells, showed higher resistance to chemotherapeutic agents such as paclitaxel and doxorubicin. HMGA1 knockdown in spheroid cells reduced the proliferative advantage and spheroid-forming efficiency of the cells and the expression of stemness-related genes. HMGA1 overexpression in adherent A2780 cells increased cancer stem cell properties, including proliferation, spheroid-forming efficiency and the expression of stemness-related genes. In addition, HMGA1 regulated ABCG2 promoter activity through HMGA1-binding sites. Knockdown of HMGA1 in spheroid cells reduced resistance to chemotherapeutic agents, whereas the overexpression of HMGA1 in adherent ovarian cancer cells increased resistance to chemotherapeutic agents in vitro. Furthermore, HMGA1-overexpressing A2780 cells showed a significant survival advantage after chemotherapeutic agent treatment in a xenograft tumorigenicity assay. Together, our results provide novel insights regarding the critical role of HMGA1 in the regulation of the cancer stem cell characteristics of ovarian cancer cells, thus suggesting that HMGA1 may be an important target in the development of therapeutics for ovarian cancer patients. More... »

PAGES

e255-e255

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/emm.2016.73

DOI

http://dx.doi.org/10.1038/emm.2016.73

DIMENSIONS

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PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/27561949


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31 schema:description Cancer stem cells are a subpopulation of cancer cells characterized by self-renewal ability, tumorigenesis and drug resistance. The aim of this study was to investigate the role of HMGA1, a chromatin remodeling factor abundantly expressed in many different cancers, in the regulation of cancer stem cells in ovarian cancer. Spheroid-forming cancer stem cells were isolated from A2780, SKOV3 and PA1 ovarian cancer cells by three-dimensional spheroid culture. Elevated expression of HMGA1 was observed in spheroid cells along with increased expression of stemness-related genes, such as SOX2, KLF4, ALDH, ABCB1 and ABCG2. Furthermore, spheroid A2780 cells, compared with adherent cells, showed higher resistance to chemotherapeutic agents such as paclitaxel and doxorubicin. HMGA1 knockdown in spheroid cells reduced the proliferative advantage and spheroid-forming efficiency of the cells and the expression of stemness-related genes. HMGA1 overexpression in adherent A2780 cells increased cancer stem cell properties, including proliferation, spheroid-forming efficiency and the expression of stemness-related genes. In addition, HMGA1 regulated ABCG2 promoter activity through HMGA1-binding sites. Knockdown of HMGA1 in spheroid cells reduced resistance to chemotherapeutic agents, whereas the overexpression of HMGA1 in adherent ovarian cancer cells increased resistance to chemotherapeutic agents in vitro. Furthermore, HMGA1-overexpressing A2780 cells showed a significant survival advantage after chemotherapeutic agent treatment in a xenograft tumorigenicity assay. Together, our results provide novel insights regarding the critical role of HMGA1 in the regulation of the cancer stem cell characteristics of ovarian cancer cells, thus suggesting that HMGA1 may be an important target in the development of therapeutics for ovarian cancer patients.
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42 ABCG2 promoter activity
43 ALDH
44 HMGA1
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46 HMGA1 overexpression
47 KLF4
48 SKOV3
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50 ability
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52 addition
53 adherent cells
54 advantages
55 agent treatment
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59 cancer
60 cancer cells
61 cancer patients
62 cancer stem cell characteristics
63 cancer stem cell properties
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65 cell characteristics
66 cell properties
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68 characteristics
69 chemotherapeutic agent treatment
70 chemotherapeutic agents
71 chromatin
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74 culture
75 development
76 development of therapeutics
77 different cancers
78 doxorubicin
79 drug resistance
80 efficiency
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82 expression
83 factors
84 genes
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87 insights
88 knockdown
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90 novel insights
91 ovarian cancer
92 ovarian cancer cells
93 ovarian cancer patients
94 ovarian cancer stem cells
95 overexpression
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97 paclitaxel
98 patients
99 proliferation
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101 promoter activity
102 properties
103 regulation
104 resistance
105 results
106 role
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