Insulin-like growth factor-1 signaling in the tumor microenvironment: Carcinogenesis, cancer drug resistance, and therapeutic potential

Kamdje, Armel Hervé Nwabo; Etet, Paul Faustin Seke; Kipanyula, Maulilio J.; Vecchio, Lorella; Tagne, Richard Simo; Njamnshi, Alfred K.; Lukong, Kiven Erique; Mimche, Patrice N.

doi:10.3389/fendo.2022.927390

Cited by 21 publications

(14 citation statements)

References 79 publications

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“…Therefore, this axis is a potential target for multiple lines of therapy, being incriminated also in tumor resistance and invasiveness. Silencing the IGF pathway has shown promising results in preclinical trials, albeit with significant challenges [ 3 , 4 ].…”

Section: Introductionmentioning

confidence: 99%

Let-7 microRNAs Are Possibly Associated with Perineural Invasion in Colorectal Cancer by Targeting IGF Axis

Niculae

Dobre

Herlea

et al. 2022

Life

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Increased insulin-like growth factor (IGF) axis activity is associated with the development and progression of different types of malignancies, including colorectal cancer (CRC). MicroRNAs (miRNAs) belonging to the let-7 family have been reported to target genes involved in this axis and are known as tumor suppressors. In this study, in silico bioinformatic analysis was performed to assess miRNA–mRNA interactions between eight miRNAs belonging to the let-7 family and genes involved in the IGF signaling pathway, coding for receptors and substrates. miRNAs’ expression analysis revealed that hsa-let-7a-5p, hsa-let-7b-5p, hsa-let-7c-5p, hsa-let- 97 7d-5p, hsa-let-7e-5p, hsa-let-7f-5p, and hsa-let-7g-5p were significantly down-regulated in 25 CRC tumoral tissues (T) compared to the corresponding adjacent peritumoral tissues (PT). Moreover, our results showed an upregulation of miR-let-7e-5p in CRC tissues with mutations in KRAS codon 12 or 13, and, for the first time, found a specific dysregulation of let-7a-5p, let-7b-5p, let-7c-5p, let-7d-5p, and let-7i-5p in CRC with perineural invasion. Our results sustain the relationship between the IGF axis, let-7 miRNAs, and CRC and suggest an association between the expression of these miRNAs and perineural invasion.

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Section: Introductionmentioning

confidence: 99%

Let-7 microRNAs Are Possibly Associated with Perineural Invasion in Colorectal Cancer by Targeting IGF Axis

Niculae

Dobre

Herlea

et al. 2022

Life

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“…IGF1R plays a crucial role in cell biology processes such as cell proliferation, metabolism, and tumor development by activating downstream signaling pathways upon binding to insulin‐like growth factor 1 (IGF‐1) or insulin‐like growth factor 2 (IGF‐2) 37,38 . Recently, IGF1R has been reported to promote cancer metastasis and drug resistance 39,40 . Patients with high IGF1R expression tend to have shorter overall survival and a higher possibility of metastasis in various types of cancer, such as breast cancer, prostate cancer, and lung cancer 41–43 .…”

Section: Discussionmentioning

confidence: 99%

Phospholysine phosphohistidine inorganic pyrophosphate phosphatase suppresses insulin‐like growth factor 1 receptor expression to inhibit cell adhesion and proliferation in gastric cancer

Zhang,

Wang,

Liu

et al. 2024

MedComm

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Phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) has recently emerged as a novel tumor suppressor. Researchers have observed that LHPP plays a crucial role in inhibiting proliferation, growth, migration, invasion, and cell metabolism across various cancers. Nevertheless, the specific functions and underlying mechanisms of LHPP as a tumor suppressor in gastric cancer (GC) require further exploration. The expression of LHPP was assessed in human GC specimens and cell lines. Various assays were employed to evaluate the impact of LHPP on GC cells. RNA sequencing and Gene Set Enrichment Analysis were conducted to unravel the mechanism through which LHPP regulates GC cell behavior. Additionally, xenograft nude mouse models were utilized to investigate the in vivo effects of LHPP. The findings indicate that LHPP, functioning as a tumor suppressor, is downregulated in both GC tissues and cells. LHPP emerges as an independent risk factor for GC patients, and its expression level exhibits a positive correlation with patient prognosis. LHPP exerts inhibitory effects on the adhesion and proliferation of GC cells by suppressing the expression of insulin‐like growth factor 1 receptor (IGF1R) and modulating downstream signaling pathways. Consequently, LHPP holds potential as a biomarker for targeted therapy involving IGF1R inhibition in GC patients.

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“…The direct effects are linked to the activation of the PI3K/AKT/mTORC1 signaling pathway, stimulated by IGF-1 and IGF-1 receptor (IGF1R) activation. Activation of this signaling pathway increases mitogenesis and cell cycle progression but protects against different apoptotic stresses [ 58 , 59 ]. Sustained proliferation and evading apoptosis are critical hallmarks of cancers [ 60 ].…”

Section: Potential Milk-related Factors Promoting Dlbclmentioning

confidence: 99%

Potential Pathogenic Impact of Cow’s Milk Consumption and Bovine Milk-Derived Exosomal MicroRNAs in Diffuse Large B-Cell Lymphoma

Melnik

Stadler

Weiskirchen

et al. 2023

IJMS

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Epidemiological evidence supports an association between cow’s milk consumption and the risk of diffuse large B-cell lymphoma (DLBCL), the most common non-Hodgkin lymphoma worldwide. This narrative review intends to elucidate the potential impact of milk-related agents, predominantly milk-derived exosomes (MDEs) and their microRNAs (miRs) in lymphomagenesis. Upregulation of PI3K-AKT-mTORC1 signaling is a common feature of DLBCL. Increased expression of B cell lymphoma 6 (BCL6) and suppression of B lymphocyte-induced maturation protein 1 (BLIMP1)/PR domain-containing protein 1 (PRDM1) are crucial pathological deviations in DLBCL. Translational evidence indicates that during the breastfeeding period, human MDE miRs support B cell proliferation via epigenetic upregulation of BCL6 (via miR-148a-3p-mediated suppression of DNA methyltransferase 1 (DNMT1) and miR-155-5p/miR-29b-5p-mediated suppression of activation-induced cytidine deaminase (AICDA) and suppression of BLIMP1 (via MDE let-7-5p/miR-125b-5p-targeting of PRDM1). After weaning with the physiological termination of MDE miR signaling, the infant’s BCL6 expression and B cell proliferation declines, whereas BLIMP1-mediated B cell maturation for adequate own antibody production rises. Because human and bovine MDE miRs share identical nucleotide sequences, the consumption of pasteurized cow’s milk in adults with the continued transfer of bioactive bovine MDE miRs may de-differentiate B cells back to the neonatal “proliferation-dominated” B cell phenotype maintaining an increased BLC6/BLIMP1 ratio. Persistent milk-induced epigenetic dysregulation of BCL6 and BLIMP1 expression may thus represent a novel driving mechanism in B cell lymphomagenesis. Bovine MDEs and their miR cargo have to be considered potential pathogens that should be removed from the human food chain.

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Insulin-like growth factor-1 signaling in the tumor microenvironment: Carcinogenesis, cancer drug resistance, and therapeutic potential

Cited by 21 publications

References 79 publications

Let-7 microRNAs Are Possibly Associated with Perineural Invasion in Colorectal Cancer by Targeting IGF Axis

Let-7 microRNAs Are Possibly Associated with Perineural Invasion in Colorectal Cancer by Targeting IGF Axis

Phospholysine phosphohistidine inorganic pyrophosphate phosphatase suppresses insulin‐like growth factor 1 receptor expression to inhibit cell adhesion and proliferation in gastric cancer

Potential Pathogenic Impact of Cow’s Milk Consumption and Bovine Milk-Derived Exosomal MicroRNAs in Diffuse Large B-Cell Lymphoma

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