Role of Insulin-like Growth Factor 1 Receptor Signaling in Stem Cell Stemness and Therapeutic Efficacy

Teng, Chiao-Fang; Jeng, Long-Bin; Shyu, Woei Cherng

doi:10.1177/0963689718779777

Cited by 31 publications

(27 citation statements)

References 71 publications

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“…However, this central role of mitophagy in the differentiation of various cell types enables mitophagic processes to induce de-differentiation of otherwise fully differentiated cells in cancer progression, allowing cancer cells to acquire stemness features [53]. Interestingly, the IGF-1 signalling pathway has been proposed to maintain both stem-like qualities and to enhance cell survival during cell differentiation [54,55].…”

Section: Discussionmentioning

confidence: 99%

IGF-1 Signalling Regulates Mitochondria Dynamics and Turnover through a Conserved GSK-3β–Nrf2–BNIP3 Pathway

Riis

Murray

O’Connor

2020

Cells

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The Insulin-like Growth Factor I (IGF-1) signalling pathway is essential for cell growth and facilitates tumourogenic processes. We recently reported that IGF-1 induces a transcriptional programme for mitochondrial biogenesis, while also inducing expression of the mitophagy receptor BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3), suggesting that IGF-1 has a key mitochondria-protective role in cancer cells. Here, we investigated this further and delineated the signaling pathway for BNIP3 induction. We established that IGF-1 induced BNIP3 expression through a known AKT serine/threonine kinase 1 (AKT)-mediated inhibitory phosphorylation on Glycogen Synthase Kinase-3β (GSK-3β), leading to activation of Nuclear Factor Erythroid 2-related Factor 2 (NFE2L2/Nrf2) and acting through the downstream transcriptional regulators Nuclear Respiratory Factor-1 (NRF1) and Hypoxia-inducible Factor 1 subunit α (HIF-1α). Suppression of IGF-1 signaling, Nrf2 or BNIP3 caused the accumulation of elongated mitochondria and altered the mitochondrial dynamics. IGF-1R null Mouse Embryonic Fibroblasts (MEFs) were impaired in the BNIP3 expression and in the capacity to mount a cell survival response in response to serum deprivation or mitochondrial stress. IGF-1 signalling enhanced the cellular capacity to induce autophagosomal turnover in response to activation of either general autophagy or mitophagy. Overall, we conclude that IGF-1 mediated a mitochondria-protective signal that was coordinated through the cytoprotective transcription factor Nrf2. This pathway coupled mitochondrial biogenesis with BNIP3 induction, and increased the cellular capacity for autophagosome turnover, whilst enhancing survival under conditions of metabolic or mitochondrial stress.

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Section: Discussionmentioning

confidence: 99%

IGF-1 Signalling Regulates Mitochondria Dynamics and Turnover through a Conserved GSK-3β–Nrf2–BNIP3 Pathway

Riis

Murray

O’Connor

2020

Cells

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“…IGF-I, mainly produced in liver, has been identified as being involved in a variety of physiological processes, such as metabolism, cell proliferation and differentiation (Yakar et al, 2002). Interestingly, IGF-I has been known to be an important component of MSCs niche exerting a major influence on proliferation and differentiation of them toward lineages of all three germ layers (Youssef et al, 2017;Teng et al, 2018). However, regarding the role of IGF-I in liver function and differentiation, much still remain to be determined.…”

Section: Discussionmentioning

confidence: 99%

Insulin‐like growth factor‐I promotes hepatic differentiation of human adipose tissue‐derived stem cells

Azandaryani

Davoodian

Samiei

et al. 2019

Cell Biology International

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There are numerous studies which provide support for the use of human adipose tissue-derived stem cells (hASCs) to generate hepatocyte-like cells. However, the produced cells exhibit only a certain level of differentiation, mainly due to inefficient induction conditions. Therefore, based on the important role of insulin-like growth factor (IGF-I) in hepatic function and development, in the current study we evaluated the differentiation efficacy of the mentioned factor to induce hASCs into functional hepatocyte-like cells. To investigate this, using a two-step protocol, hASCs were treated with a combination of HGF, Dex, and OSM in the presence or absence of IGF-I up to 21 days. Hepatic differentiation was evaluated by analyzing specific hepatocyte markers at different time points of differentiation induction. Increased expression of hepatocyte-specific genes including ALB, AFP, CK18, and HNF4a, downregulation of bile duct cells marker (CK19), the higher number of ALB positive cells, increased urea production together with higher glycogen deposit was observed upon the treatment of hASCs with the induction medium containing IGF-I compared to the other treatment. In conclusion, our findings suggest IGF-I as a potent inducer of hepatic differentiation of hASCs and its potential to generate more functional hepatocyte-like cells.

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“…Insulin is a hormone commonly used for in vitro stem cell cultures, which promotes stem cell survival and self‐renewal (Godoy‐Parejo, Deng, Liu, & Chen, 2019). IGFs, which belong to the insulin superfamily, also have roles in stemness maintenance in vitro (Teng, Jeng, & Shyu, 2018). It has been observed that increased IGF‐1 levels in satellite cells lead to their rapid expansion during skeletal muscle regeneration, indicating their trophic role in muscle stem cells in vivo (Jennische, Skottner, & Hansson, 1987).…”

Section: In Vitro Culture Of Muscle Stem Cellsmentioning

confidence: 99%

Muscle stem cell isolation and in vitro culture for meat production: A methodological review

Choi

Yoon

Kim

et al. 2020

Comp Rev Food Sci Food Safe

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Cultured muscle tissue‐based protein products, also known as cultured meat, are produced through in vitro myogenesis involving muscle stem cell culture and differentiation, and mature muscle cell processing for flavor and texture. This review focuses on the in vitro myogenesis for cultured meat production. The muscle stem cell–based in vitro muscle tissue production consists of a sequential process: (1) muscle sampling for stem cell collection, (2) muscle tissue dissociation and muscle stem cell isolation, (3) primary cell culture, (4) upscaled cell culture, (5) muscle differentiation and maturation, and (6) muscle tissue harvest. Although muscle stem cell research is a well‐established field, the majority of these steps remain to be underoptimized to enable the in vitro creation of edible muscle‐derived meat products. The profound understanding of the process would help not only cultured meat production but also business sectors that have been seeking new biomaterials for the food industry. In this review, we discuss comprehensively and in detail each step of cutting‐edge methods for cultured meat production. This would be meaningful for both academia and industry to prepare for the new era of cellular agriculture.

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Role of Insulin-like Growth Factor 1 Receptor Signaling in Stem Cell Stemness and Therapeutic Efficacy

Cited by 31 publications

References 71 publications

IGF-1 Signalling Regulates Mitochondria Dynamics and Turnover through a Conserved GSK-3β–Nrf2–BNIP3 Pathway

IGF-1 Signalling Regulates Mitochondria Dynamics and Turnover through a Conserved GSK-3β–Nrf2–BNIP3 Pathway

Insulin‐like growth factor‐I promotes hepatic differentiation of human adipose tissue‐derived stem cells

Muscle stem cell isolation and in vitro culture for meat production: A methodological review

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