Addiction to the IGF2-ID1-IGF2 circuit for maintenance of the breast cancer stem-like cells

Tominaga, Kunihiko; Shimamura, Teppei; Kimura, Natsuko; Murayama, Takahiko; Matsubara, Daisuke; Kanauchi, Hajime; Niida, Atushi; Shimizu, Satoshi; Nishioka, Koki; Tsuji, Ei ichi; Yano, Masao; Sugano, Sumio; Shimono, Yohei; Ishii, Hideshi; Saya, Hideyuki; Mori, Masaki; Akashi, Koichi; Tada, Kei ichiro; Ogawa, Toshihisa; Tojo, Arinobu; Miyano, Satoru; Gotoh, Noriko

doi:10.1038/onc.2016.293

Cited by 60 publications

(49 citation statements)

References 49 publications

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“…In line with this, 5azacytidine treatment inhibited rhabdomyosarcoma cell growth through repression of IGF2 expression and re-expression of H19 in vitro [150]. Additionally, it has been shown that IGF2 can maintain cancer stem cell populations in breast cancer [151] and HCC [152]. However, maintenance of cancer stem cell population seems to be more dependent on IGF1R, the previously discussed healthy stem cells signaling primarily through IRA [153].…”

Section: Igf2 Targeting In Cancer and Therapy Resistancesupporting

confidence: 54%

Insulin-Like Growth Factor 2 in Physiology, Cancer, and Cancer Treatment

Röttgering¹,

Szuhai²

2019

obm genet

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Insulin-like growth factor 2 (IGF2) is a strong mitogenic peptide with an imprinted gene that is primarily involved in fetal development. It is highly expressed in the fetus where it is involved in fetal growth and tissue differentiation. However, postnatally, the expression of IGF2 decreases despite higher expression levels in the blood as compared with that of IGF1. In adults, the physiological function of IGF2 is poorly understood; however, the possibility of a metabolic function exists. Although the expression of IGF2 normally decreases in adults, it is overexpressed in a variety of cancers and associated with increased insulin-like growth factor 1 (IGF1R) receptor and insulin receptor (IR) activity. This subsequently increases the activity of downstream genes such as AKT, FOXO, and MAPK, resulting in enhanced proliferation, survival, and overall worse prognosis in patients overexpressing IGF2. As IGF1R activation has been found in several types of cancers, many different IGF1R-targeted therapies have been clinically evaluated, however, with only limited anti-cancer efficacy. In the present review, the physiological function of IGF2 will be outlined in relation to gene expression, imprinting, and signaling. Additionally, differences in physiological and aberrant signaling of IGF2 in cancer will be summarized.

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Section: Igf2 Targeting In Cancer and Therapy Resistancesupporting

confidence: 54%

Insulin-Like Growth Factor 2 in Physiology, Cancer, and Cancer Treatment

Röttgering¹,

Szuhai²

2019

obm genet

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“…Mammospheres have been used to examine intertumoral heterogeneity and determine the proliferative roles of the interleukin‐8/C‐X‐C motif chemokine receptor 1/2‐mediated pathway and insulin‐like growth factor 2 pathway . In another study, established mammospheres were used to examine the specific effects chemical compounds have against CSCs .…”

Section: Spheroid Cultures From Primary Cancersmentioning

confidence: 99%

“…(39) Mammospheres have been used to examine intertumoral heterogeneity (40,41) and determine the proliferative roles of the interleukin-8/C-X-C motif chemokine receptor 1/2-mediated pathway (38) and insulin-like growth factor 2 pathway. (42) In another study, established mammospheres were used to examine the specific effects chemical compounds have against CSCs. (43) Mammosphere assays were also used for a mouse breast cancer model of Erb-B2 receptor tyrosine kinase 2 expression (44) and p53-deficiency.…”

Section: Spheroid Cultures From Primary Cancersmentioning

confidence: 99%

Tumor‐derived spheroids: Relevance to cancer stem cells and clinical applications

Ishiguro

Ohata²,

Sato³

et al. 2017

Cancer Science

409

326

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Recently, many types of in vitro 3‐D culture systems have been developed to recapitulate the in vivo growth conditions of cancer. The cancer 3‐D culture methods aim to preserve the biological characteristics of original tumors better than conventional 2‐D monolayer cultures, and include tumor‐derived organoids, tumor‐derived spheroids, organotypic multicellular spheroids, and multicellular tumor spheroids. The 3‐D culture methods differ in terms of cancer cell sources, protocols for cell handling, and the required time intervals. Tumor‐derived spheroids are unique because they are purposed for the enrichment of cancer stem cells (CSCs) or cells with stem cell‐related characteristics. These spheroids are grown as floating spheres and have been used as surrogate systems to evaluate the CSC‐related characteristics of solid tumors in vitro. Because eradication of CSCs is likely to be of clinical importance due to their association with the malignant nature of cancer cells, such as tumorigenicity or chemoresistance, the investigation of tumor‐derived spheroids may provide invaluable clues to fight against cancer. Spheroid cultures have been established from cancers including glioma, breast, colon, ovary, and prostate cancers, and their biological and biochemical characteristics have been investigated by many research groups. In addition to the investigation of CSCs, tumor‐derived spheroids may prove to be instrumental for a high‐throughput screening platform or for the cultivation of CSC‐related tumor cells found in the circulation or body fluids.

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“…We have also shown that PI3K/Akt signaling pathway, which is activated by heregulin, contributes to the maintenance of CSCs in breast cancer [101] . Insulin-like growth factor-2 (IGF-2) [102] and growth differentiation factor 15 (GDF15) [103] , downstream factors of heregulin/PI3K/Akt, have been shown to play important roles in CSC maintenance [ Figure 4]. MAPK-ERK signaling pathway is also important for CSC maintenance.…”

Section: Treatment Approaches Targeting Other Activated Signaling Patmentioning

confidence: 99%

Drug resistance mechanisms of cancer stem-like cells and their therapeutic potential as drug targets

Murayama¹,

Gotoh²

2019

CDR

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Despite of recent advances in cancer research and development of new anti-cancer drugs, tumor patients' prognoses have not yet been improved well enough. Treatment failure of tumors is highly attributed to the drug resistance of a small population of cancer cell known as cancer stem-like cells (CSCs). CSCs also have the self-renewal activity and differentiation potency, conferring strong tumorigenicity on them. Therefore, development of CSC targeting therapy is urgently needed in order to overcome possible recurrence and metastasis by them after therapy. CSCs show some characteristic features that are not observed in other differentiated cancer cells, which give them higher resistance against conventional chemotherapy or radiotherapy. Targeting such specific features could be useful for CSC eradication. This review will summarize the recent advances in the study of CSC characteristics along with the promising therapeutic strategies targeting them.

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Addiction to the IGF2-ID1-IGF2 circuit for maintenance of the breast cancer stem-like cells

Cited by 60 publications

References 49 publications

Insulin-Like Growth Factor 2 in Physiology, Cancer, and Cancer Treatment

Insulin-Like Growth Factor 2 in Physiology, Cancer, and Cancer Treatment

Tumor‐derived spheroids: Relevance to cancer stem cells and clinical applications

Drug resistance mechanisms of cancer stem-like cells and their therapeutic potential as drug targets

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