PIK3R1 negatively regulates the epithelial-mesenchymal transition and stem-like phenotype of renal cancer cells through the AKT/GSK3β/CTNNB1 signaling pathway

Lin, You-Cheng; Zhao, Yanping; Xu, Aiming; Dong, Pei; Huang, Yi; Liu, Huan; Li, Feida; Wang, Haifeng; Xu, Qian; Wang, Yongqiang; Sun, Da; Zou, Yong; Zou, Xiaowen; Wang, Yu; Zhang, Duo; Liu, Hongjie; Wu, Xun; Zhang, Meng; Fu, Yu; Cai, Zhiming; Liu, Chunxiao; Wu, Song

doi:10.1038/srep08997

Cited by 60 publications

(52 citation statements)

References 45 publications

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“…In this RCC model the vast majority (122/160) of genes induced by hypoxia in wt-VHL transfected 786-O ( VHL + ) cells are not significantly up-regulated in VHL mutated 786-O cells, confirming that the loss of VHL is not equivalent to hypoxic exposure and that in RCC, the VHL tumor suppressor has a distinct role from its activity in the hypoxia-inducible pathway [57]. Interestingly, side populations (SPs) of higher tumorigenicity were observed in this cell line, proving its usefulness in cancer stem cell studies [58, 59]. Surface receptors also confirm the ccRCC phenotype of 786-O cells, as these cells are positive for CD10 [60] and vimentin [61].…”

Section: Introductionmentioning

confidence: 70%

Choosing the right cell line for renal cell cancer research

Brodaczewska¹,

Szczylik²,

et al. 2016

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Cell lines are still a tool of choice for many fields of biomedical research, including oncology. Although cancer is a very complex disease, many discoveries have been made using monocultures of established cell lines. Therefore, the proper use of in vitro models is crucial to enhance our understanding of cancer. Therapeutics against renal cell cancer (RCC) are also screened with the use of cell lines. Multiple RCC in vitro cultures are available, allowing in vivo heterogeneity in the laboratory, but at the same time, these can be a source of errors. In this review, we tried to sum up the data on the RCC cell lines used currently. An increasing amount of data on RCC shed new light on the molecular background of the disease; however, it revealed how much still needs to be done. As new types of RCC are being distinguished, novel cell lines and the re-exploration of old ones seems to be indispensable to create effective in vitro tools for drug screening and more.Electronic supplementary materialThe online version of this article (doi:10.1186/s12943-016-0565-8) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 70%

Choosing the right cell line for renal cell cancer research

Brodaczewska¹,

Szczylik²,

et al. 2016

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“…Notch2+ human pancreatic cancer Bxpc-3 and Panc-1 cells have properties of CSCs, which have a strong tumourigenic ability (Zhou et al, 2013). Depletion of CTNNB1 impaired the stem-like phenotype of renal cell carcinoma (Lin et al, 2015). Indeed, the WNT/CTNNB1 signaling is involved in regulating many types of stem cells (He K. et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

miR-150 Suppresses the Proliferation and Tumorigenicity of Leukemia Stem Cells by Targeting the Nanog Signaling Pathway

Zhou

Wang

et al. 2016

Front. Pharmacol.

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Proliferation, a key feature of cancer cells, accounts for the majority of cancer-related diseases resulting in mortality. MicroRNAs (miRNAs) plays important post-transcriptional modulation roles by acting on multiple signaling pathways, but the underlying mechanism in proliferation and tumorigenicity is unclear. Here, we identified the role of miR-150 in proliferation and tumorigenicity in leukemia stem cells (LSCs; CD34+CD38- cells). miR-150 expression was significantly down-regulated in LSCs from leukemia cell lines and clinical samples. Functional assays demonstrated that increased miR-150 expression inhibited proliferation and clonal and clonogenic growth, enhanced chemosensitivity, and attenuated tumorigenic activity of LSCs in vitro. Transplantation animal studies revealed that miR-150 overexpression progressively abrogates tumor growth. Immunohistochemistry assays demonstrated that miR-150 overexpression enhanced caspase-3 level and reduced Ki-67 level. Moreover, luciferase reporter assays indicated Nanog is a direct and functional target of miR-150. Nanog silencing using small interfering RNA recapitulated anti-proliferation and tumorigenicity inhibition effects. Furthermore, miR-150 directly down-regulated the expression of other cancer stem cell factors including Notch2 and CTNNB1. These results provide insights into the specific biological behavior of miR-150 in regulating LSC proliferation and tumorigenicity. Targeting this miR-150/Nanog axis would be a helpful therapeutic strategy to treat acute myeloid leukemia.

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“…CD133+ cells isolated from primary tumors (nephrectomy specimens) of RCC were shown to promote tumor vascularization and neoangiogenesis in the nude mice model [37]. In another trial, CD133+/CD24+/CTR2+ cells were tumorigenic and indicated as RCC CSCs/TICs [55], as well as CD44+/CD133+/CXCR4+ [49] and CD44+/CD105+/CD133+/CD90+ cells [56]. In our study, CD133 was expressed at low levels in established RCC cell lines, which is in accordance with previous data [38, 57].…”

Section: Discussionmentioning

confidence: 99%

Functional significance of CD105-positive cells in papillary renal cell carcinoma

Matak

Brodaczewska²,

Szczylik³

et al. 2017

BMC Cancer

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BackgroundCD105 was postulated as a renal cell carcinoma (RCC) stem cell marker, and CD133 as a putative RCC progenitor. Hypoxia, a natural microenvironment that prevails in tumors, was also incorporated into the study, especially in terms of the promotion of hypothetical stem-like cell properties.MethodsWithin this study, we verify the existence of CD105+ and CD133+ populations in selected papillary subtype RCC (pRCC) cell lines. Both populations were analyzed for correlation with stem-like cell properties, such as stemness gene expression, and sphere and colony formation. For the preliminary analysis, several RCC cell lines were chosen (786-O, SMKT-R2, Caki-2, 796-P, ACHN, RCC6) and the control was human kidney cancer stem cells (HKCSC) and renal cells of embryonic origin (ASE-5063). Four cell lines were chosen for further investigation: Caki-2 (one of the highest numbers of CD105+ cells; primary origin), ACHN (a low number of CD105+ cells; metastatic origin), HKCSC (putative positive control), and ASE-5063 (additional control).ResultsIn 769-P and RCC6, we could not detect a CD105+ population. Hypoxia variously affects pRCC cell growth, and mainly diminishes the stem-like properties of cells. Furthermore, we could not observe the correlation of CD105 and/or CD133 expression with the enhancement of stem-like properties.ConclusionsBased on this analysis, CD105/CD133 cannot be validated as cancer stem cell markers of pRCC cell lines.

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PIK3R1 negatively regulates the epithelial-mesenchymal transition and stem-like phenotype of renal cancer cells through the AKT/GSK3β/CTNNB1 signaling pathway

Cited by 60 publications

References 45 publications

Choosing the right cell line for renal cell cancer research

Choosing the right cell line for renal cell cancer research

miR-150 Suppresses the Proliferation and Tumorigenicity of Leukemia Stem Cells by Targeting the Nanog Signaling Pathway

Functional significance of CD105-positive cells in papillary renal cell carcinoma

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