Silencing of CD133 inhibits GLUT1‐mediated glucose transport through downregulation of the HER3/Akt/mTOR pathway in colon cancer

Kim, Hyungjoo; Ju, Ji-hyun; Son, Sang Jun; Shin, Incheol

doi:10.1002/1873-3468.13686

Cited by 7 publications

(5 citation statements)

References 57 publications

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“…CD133 avoids EGFR endocytosis and sustains EGFR-mediated Akt activation [ 68 , 69 ]. CD133 silencing decreases HER3 levels and suppresses EGFR and HER2 activation without disturbing their gene transcription in CRC cell lines [ 70 ]. CD133 silencing reduces proliferation, clonogenic capacity, migration, cell invasion, and resistance in CRC in part through decreasing glucose uptake as a result of the low GLUT1 expression because of impaired HER3/Akt pathway involved in protein synthesis via mTOR and mRNA stability, probably through the regulation of RNA-binding proteins [ 70 , 71 ].…”

Section: Cd133 Biological Function (Signaling Pathways)mentioning

confidence: 99%

“…CD133 silencing decreases HER3 levels and suppresses EGFR and HER2 activation without disturbing their gene transcription in CRC cell lines [ 70 ]. CD133 silencing reduces proliferation, clonogenic capacity, migration, cell invasion, and resistance in CRC in part through decreasing glucose uptake as a result of the low GLUT1 expression because of impaired HER3/Akt pathway involved in protein synthesis via mTOR and mRNA stability, probably through the regulation of RNA-binding proteins [ 70 , 71 ]. Enrichment RNA analysis showed that CD133 + cells in gastric cancer have high expression of RNA-modifying enzymes that modulate RNA decay, mRNA translation, pre-mRNA processing, and RNA export compared to CD133-negative cells [ 72 ]; however, the precise role of CD133 in mRNA processing is unclear.…”

Section: Cd133 Biological Function (Signaling Pathways)mentioning

confidence: 99%

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Functional Roles of CD133: More than Stemness Associated Factor Regulated by the Microenvironment

Moreno-Londoño,

Robles-Flores

2023

Stem Cell Rev and Rep

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CD133 protein has been one of the most used surface markers to select and identify cancer cells with stem-like features. However, its expression is not restricted to tumoral cells; it is also expressed in differentiated cells and stem/progenitor cells in various normal tissues. CD133 participates in several cellular processes, in part orchestrating signal transduction of essential pathways that frequently are dysregulated in cancer, such as PI3K/Akt signaling and the Wnt/β-catenin pathway. CD133 expression correlates with enhanced cell self-renewal, migration, invasion, and survival under stress conditions in cancer. Aside from the intrinsic cell mechanisms that regulate CD133 expression in each cellular type, extrinsic factors from the surrounding niche can also impact CD33 levels. The enhanced CD133 expression in cells can confer adaptive advantages by amplifying the activation of a specific signaling pathway in a context-dependent manner. In this review, we do not only describe the CD133 physiological functions known so far, but importantly, we analyze how the microenvironment changes impact the regulation of CD133 functions emphasizing its value as a marker of cell adaptability beyond a cancer-stem cell marker. Graphical Abstract

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Section: Cd133 Biological Function (Signaling Pathways)mentioning

confidence: 99%

Section: Cd133 Biological Function (Signaling Pathways)mentioning

confidence: 99%

Functional Roles of CD133: More than Stemness Associated Factor Regulated by the Microenvironment

Moreno-Londoño,

Robles-Flores

2023

Stem Cell Rev and Rep

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“…45 S6K1 acts as the core effector protein downstream of AKT, mediating protein transcription and positively correlates with the activity of AKT signaling. 46,47 However, whether activation of AKT signaling results in aberrant GLUT1 expression in GC still needs to be elucidated.…”

Section: Dovepressmentioning

confidence: 99%

“…26 Furthermore, an apparent positive association between GLUT1 and p-S6K1 indicated that the AKT-S6K1 axis plays a role in the effect of GLUT1 on GC. 46,[49][50][51] Subgroup survival analysis of GC patients based on p-S6K1 and GLUT1 expression showed that GLUT1 overexpression could be the governing factor upstream of AKT-S6K1. Because GC patients with p-S6K1(+) had worse prognosis than those with p-S6K1(-), GLUT1(+)/p-S6K1(+) also showed a lower survival probability to patients who showed a low negative expression of GLUT1 or p-S6K1.…”

Section: Dovepressmentioning

confidence: 99%

<p>Glucose Transporter-1 Cooperating with AKT Signaling Promote Gastric Cancer Progression</p>

Zhou¹,

Jiang²,

Jin³

et al. 2020

CMAR

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High expression of GLUT1 has been observed in numerous solid cancers, facilitating glucose consumption for supporting tumor cell survival. The altered metabolic activity is regulated by series of signaling pathways, including AKT signaling that acts as a key role in glucose metabolism and shows close correlation with the malignant transformation. In this study, we aimed to elucidate the effect of GLUT1 on gastric cancer (GC) and to explore the relation between GLUT1 and AKT signaling. Materials and Methods: GLUT1, p-AKT, and p-S6k1 expression were investigated by immunohistochemistry and semi-quantitative analysis in 57 paired-GC samples. The relationship of GLUT1 with clinical indexes in GC tissues was investigated. The effects of GLUT1 on the prognosis of GC patients and the underlying mechanism involved were studied by subgroup analysis. Results: In GC tissues, an obvious increase in GLUT1 expression was observed when compared with that of normal tissues (P<0.001). Advanced clinicopathological factors (tumor size P=0.019, invasion depth P=0.002, lymph node metastasis P<0.001, differentiation P=0.024, neural invasion P=0.003, and TNM staging P=0.001) correlated with high GLUT1 levels. GLUT1 was an independent risk factor resulting in poor prognosis (P=0.002, HR=5.132). GLUT1 increased the activation ratio of p-AKT (P<0.01) and p-S6K1 (P<0.001) in GC. The expression of p-S6K1 and GLUT1 was positively correlated. (P=0.001, R=0.173). The survival probability of GC patients with GLUT1(+)/p-S6K1(+) was worse when compared to that of GLUT1(+)/p-S6K1(-) or GLUT1 (-)/p-S6K1(+) (P<0.001). Conclusion: High expression of GLUT1 facilitated GC progression, leading to poor prognosis. Overexpression of GLUT1 activated AKT-S6K1 axis, resulting in adverse outcomes of GC. GLUT1 is novel indicator of GC prognosis and GLUT1 targeted metabolic treatment that has potential therapeutic value.

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“…AKT/mTOR signaling pathway suffers the most mutations in cancer, being a link between obesity and cancer (especially breast and colon) (26)(27)(28)(29). Steroid hormones, namely estrogens, progesterone, androgens and adrenal steroids are associated with obesity and the development of certain types of neoplasms in women (30).…”

Section: Obesity and Cancermentioning

confidence: 99%

Obesity induces DNA damage

Ştefani¹,

Totan²,

Miricescu³

et al. 2019

Ro Med J.

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A diet rich in saturated lipids, refined carbohydrates associated with a sedentary lifestyle leads to obesity in both adults and children. Obesity is associated with the existence of a chronic inflammatory process, that will further lead to systemic oxidative stress and DNA oxidative damage. There is currently a positive correlation between obesity and cancer due to nuclear but also mitochondrial DNA injury. Obesity is a risk factor for the development of several types of cancer such as breast, prostate or colorectal. The purpose of this review is to present the effects of obesity on human body, by describing the chronic inflammatory process, oxidative stress, and the molecular mechanisms involved in cancer progression.

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Silencing of CD133 inhibits GLUT1‐mediated glucose transport through downregulation of the HER3/Akt/mTOR pathway in colon cancer

Cited by 7 publications

References 57 publications

Functional Roles of CD133: More than Stemness Associated Factor Regulated by the Microenvironment

Functional Roles of CD133: More than Stemness Associated Factor Regulated by the Microenvironment

<p>Glucose Transporter-1 Cooperating with AKT Signaling Promote Gastric Cancer Progression</p>

Obesity induces DNA damage

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