Murine Insulin Growth Factor-like (IGFL) and Human IGFL1 Proteins Are Induced in Inflammatory Skin Conditions and Bind to a Novel Tumor Necrosis Factor Receptor Family Member, IGFLR1

Lobito, Adrian A.; Ramani, Sree R.; Tom, Irene; Bazán, J. Fernando; Luis, Elizabeth; Fairbrother, Wayne J.; Ouyang, Wenjun; Gonzalez, Lino C.

doi:10.1074/jbc.m111.224626

Cited by 38 publications

(36 citation statements)

References 47 publications

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“…IGFL1 similar to other related IGF is involved in cellular energy metabolism, growth and development, and promotion of cell division 34. IGFL1 is known to be upregulated in skin conditions such as psoriasis that promote the abnormal proliferation and differentiation of epidermal keratinocytes 35,36. Additionally, the observed increase in cell proliferation at a 1 ppm dose could be attributed to induction of cyclin D1 transcription by low-dose arsenic as reported by Hwang et al37 Cyclin D1 stimulates growth by shifting the G1 growth phase into the S/G2 cell cycle compartment.…”

Section: Discussionmentioning

confidence: 99%

Cytotoxicity patterns of arsenic trioxide exposure on HaCaT keratinocytes

Udensi

Graham‐Evans²,

Rogers³

et al. 2011

CCID

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BackgroundArsenic is a ubiquitous environmental toxicant, and abnormalities of the skin are the most common outcomes of long-term, low-dose, chronic arsenic exposure. If the balance between keratinocyte proliferation, differentiation, and death is perturbed, pathologic changes of the epidermis may result, including psoriasis, atopic dermatitis, and certain forms of ichthyosis. Therefore, research investigations using in vitro human epidermal cells could help elucidate cellular and molecular processes in keratinocytes affected by arsenic. Data from such investigations could also provide the basis for developing cosmetic intervention for skin diseases caused by arsenic.MethodsThe viability of HaCaT keratinocyte cultures with or without prior exposure to low-dose arsenic trioxide was compared for varying concentrations of arsenic trioxide over a time course of 14 days because in untreated control cultures, approximately 2 weeks is required to complete cell differentiation. Long-term cultures were established by culturing HaCaT cells on collagen IV, and cells were subsequently exposed to 0 parts per million (ppm), 1 ppm, 5 ppm, 7.5 ppm, 10 ppm, and 15 ppm of arsenic trioxide. The percentages of viable cells as well as DNA damage after exposure were determined on Day 2, Day 5, Day 8, and Day 14.ResultsUsing both statistical and visual analytics approaches for data analysis, we have observed a biphasic response at a 5 ppm dose with cell viability peaking on Day 8 in both chronic and acute exposures. Further, a low dose of 1 ppm arsenic trioxide enhanced HaCaT keratinocyte proliferation, whereas doses above 7.5 ppm inhibited growth.ConclusionThe time course profiling of arsenic trioxide cytotoxicity using long-term HaCaT keratinocyte cultures presents an approach to modeling the human epidermal cellular responses to varying doses of arsenic trioxide treatment or exposure. A low dose of arsenic trioxide appears to aid cell growth but concomitantly disrupts the DNA transcription process.

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Section: Discussionmentioning

confidence: 99%

Cytotoxicity patterns of arsenic trioxide exposure on HaCaT keratinocytes

Udensi

Graham‐Evans²,

Rogers³

et al. 2011

CCID

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“…7A and B). The expression of IGFL1, known to be enhanced by TNF (Lobito et al 2011), was up-regulated by about 14 times in H292 IR KD cells. However, the IGFL1 receptor (IGFL1R) was down-regulated in the three cell lines.…”

Section: Microarray-based Gene Expression Profiling and Correlation Tmentioning

confidence: 92%

Non-small cell lung cancer cell survival crucially depends on functional insulin receptors

Frisch

Zimmermann

Zilleßen

et al. 2015

Endocrine-Related Cancer

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Insulin plays an important role as a growth factor and its contribution to tumor proliferation is intensely discussed. It acts via the cognate insulin receptor (IR) but can also activate the IGF1 receptor (IGF1R). Apart from increasing proliferation, insulin might have additional effects in lung cancer. Therefore, we investigated insulin action and effects of IR knockdown (KD) in three (NCI-H292, NCI-H226 and NCI-H460) independent non-small cell lung cancer (NSCLC) cell lines. All lung cancer lines studied were found to express IR, albeit with marked differences in the ratio of the two variants IR-A and IR-B. Insulin activated the classical signaling pathway with IR autophosphorylation and Akt phosphorylation. Moreover, activation of MAPK was observed in H292 cells, accompanied by enhanced proliferation. Lentiviral shRNA IR KD caused strong decrease in survival of all three lines, indicating that the effects of insulin in lung cancer go beyond enhancing proliferation. Unspecific effects were ruled out by employing further shRNAs and different insulin-responsive cells (human pre-adipocytes) for comparison. Caspase assays demonstrated that IR KD strongly induced apoptosis in these lung cancer cells, providing the physiological basis of the rapid cell loss. In search for the underlying mechanism, we analyzed alterations in the gene expression profile in response to IR KD. A strong induction of certain cytokines (e.g. IL20 and tumour necrosis factor) became obvious and it turned out that these cytokines trigger apoptosis in the NSCLC cells tested. This indicates a novel role of IR in tumor cell survival via suppression of pro-apoptotic cytokines.

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“…4. This microarray was subsequently used to discover a novel interaction between a small, secreted cysteine-rich protein termed IGFL with the TNF receptor-like protein TMEM149 (renamed IGFLR1) [93].…”

Section: Glass Slide-based Protein Microarraysmentioning

confidence: 99%

“…Proteins from the SPDI library were expressed in Escherichia coli, insect or mammalian cells with either a poly-His or Fc tag and have been used to identify interactions using SPR, bio-layer interferometry and protein microarrays [53,72,73,92,93].…”

Section: Clone and Protein Library Effortsmentioning

confidence: 99%

Protein microarrays, biosensors, and cell-based methods for secretome-wide extracellular protein–protein interaction mapping

Gonzalez¹

2012

Methods

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Approximately one quarter of all human genes encode proteins that function in the extracellular space or serve to bridge the extracellular and intracellular environments. Physical associations between these secretome proteins serve to regulate a wide range of biological activities and consequently represent important therapeutic targets. Moreover, some extracellular proteins are targeted by pathogens to allow host access or immune evasion. Despite the importance of extracellular protein-protein interactions, our knowledge in this area has remained sparse. Weak affinities and low abundance have often hindered efforts to identify these interactions using traditional methods such as biochemical purification and cDNA library expression cloning. Moreover, current large-scale protein-protein interaction mapping techniques largely under represent extracellular protein-protein interactions. This review highlights emerging biosensor and protein microarray technology, along with more traditional cell-based techniques, that are compatible with secretome-wide screens for extracellular protein-protein interaction discovery. A combination of these approaches will serve to rapidly expand our knowledge of the extracellular protein-protein interactome.

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Murine Insulin Growth Factor-like (IGFL) and Human IGFL1 Proteins Are Induced in Inflammatory Skin Conditions and Bind to a Novel Tumor Necrosis Factor Receptor Family Member, IGFLR1

Cited by 38 publications

References 47 publications

Cytotoxicity patterns of arsenic trioxide exposure on HaCaT keratinocytes

Cytotoxicity patterns of arsenic trioxide exposure on HaCaT keratinocytes

Non-small cell lung cancer cell survival crucially depends on functional insulin receptors

Protein microarrays, biosensors, and cell-based methods for secretome-wide extracellular protein–protein interaction mapping

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