Cancer Letters presently published a paper entitled "KLF5-induced lncRNA IGFL2-AS1 promotes basal-like breast cancer cell growth and survival by upregulating the expression of IGFL1" [1]. The study suggested that IGFL1 as an oncogene contributes to the proliferation and growth of basal-like breast cancer cells, which provides a new idea for breast cancer targeted therapy. As a novel target, albeit IGFL1 is currently in an early stage research, many international journals have reported the key role of IGFL1 in various biological processes. These findings implied that IGFL1 might be served as a potential therapeutic target for inflammatory skin diseases and cancer. Currently, researchers are conducting more investigations for better understanding of IGFL1. To meet your desires regarding this novel target, our article will take you through to get fully knowledge about IGFL1.
IGFL1 is insulin-like growth factor-1 (Insulin growth factor-like family member 1IGFL1), which belongs to the IGF-like (IGFL) family. In 2006, Peter Emtage et al. found the new secreted family and named it IGF-like (IGFL) family. IGF-like (IGFL) gene encodes a protein of about 100 amino acids that contain 11 conserved cysteine residues at fixed positions, including two CC motifs. In humans, the IGF-like (IGFL) family contains four genes (IGFL1, IGFL2, IGFL3, and IGFL4) and two pseudogenes (IGFL1P1 and IGFL1P2). Human IGFL genes are clustered together on chromosome 19 within a 35-kb interval.
IGFL is usually not or rarely expressed in tissues. Existing data suggested that IGFL1 is not expressed in a wide range of tissues including adrenal gland, bone marrow, brain, prostate, skin, small intestine, thyroid and uterus; it is expressed in fetal skin, normal mammary gland, ovary and spinal cord. In addition, some databases showed the presence of IGFL1 expression in cancer cells, including squamous cell carcinoma, uterine tumors, and head and neck tumors, suggesting that IGFL1 is expected to be a novel potential target for cancer [2].
IGFLR1 is a receptor for IGFL1. In 2011, Adrian A. Lobito et al. discovered that human IGFL1 has high specificity and affinity with IGFLR1 (previously called TMEM149) that is structurally similar to the tumor necrosis factor receptor family (TNFRs). Therefore, IGFLR1 was identified as a receptor for IGFL1 for the first time. Also, IGFLR1 is considered a novel receptor in the TNFR family. The IGFLR1 gene is localized on chromosome 19 and is widely expressed in the lymph nodes, spleen and kidney. Adrian's study also indicates that IGFLR1 is most abundantly expressed on mouse T cells and its high expression promotes inflammatory infiltration and activation. The results implied that the IGFL1-binding receptor IGFLR1 produced by the skin could regulate the T cell responses [3].
IGFL1 and receptor IGFLR1 as emerging targets, the mechanism between the two targets remains to be understood. In 2022, a recent research found that IGFLR1 may be one of the important pathogenic factors in pancreatic ductal adenocarcinoma (PDAC). PDAC is the major tumor type of pancreatic cancer, accounting for 80% to 90% of cases. Using the Variant Annotation, Analysis & Search Tool (VAAST), researchers screened several pathogenic candidate genes, including IGFLR1, which ranked within the top 15 [4]. Another study showed that high expression levels of IGFLR1 predicted low survival in patients with clear cell carcinoma of the kidney (ccRCC). Besides, high expression of IGFLR1 was observed in both CXCL13+ BHLHE40+ TH1-like cells and CD8+ advanced T cells. Taken together, IGFLR1 may help guide the diagnosis, treatment, and prognosis of CRC [5].
Since other IGF family members are involved in varied biological metabolic processes, such as IGF1, a multifunctional regulator, IGF1 is not only involved in biological responses of cells, such as differentiation, apoptosis, migration, and survival, but also plays essential roles in growth metabolism, osteoporosis, dermatological diseases, and tumor development. Due to the structural similarity between IGFL1 protein and IGF superfamily, there may be functional similarities. Current studies have identified that IGFL1 mediates similar diseases like cellular metabolism, inflammatory skin diseases (allergic skin diseases and psoriasis), and cancers (breast and ovarian cancers, etc.).
Aforementioned, IGF1 is essential growth hormone molecule. It is very likely that IGFL1 protein may also be important in supporting growth and regulating metabolism. Apparently, the expression pattern of IGFL1 supports this hypothesis. Early findings have unrevealed that the IGFL1 gene is expressed in fetal epithelial tissues, which have a higher propensity for growth and differentiation [2].
Some studies have reported the IGFL1 as a candidate target gene for atopic dermatitis (AD) disease, which may be associated with abnormal activation of immune responses in AD patients, particularly activation of Th17 immunity, one of the key subtypes in the T-cell pathway. Atopic dermatitis is a common inflammatory skin disease. Patients with atopic dermatitis are often accompanied by imbalances in the expression levels of various cytokines, characterized by the presence of activated T-cell subtypes (Th1, Th2, Th17) in the skin. The T cell-mediated immune dysregulation is central to the pathogenesis of several inflammatory skin diseases. Activation of T-cell turn-on or off in skin diseases will influence the treatments. Therefore, targeting IGFL1 may represent a new direction for AD treatment [6, 7].
In addition, researchers have found through the GEO database that IGFL1 is upregulated in human psoriasis samples, which is considered as the Hub gene for psoriatic disease. Meanwhile, a growing body of experimental data suggests that IGFL1 is highly expressed in psoriasis affected skin. Psoriasis is a chronic proliferative and inflammatory condition of the skin. One of the most frustrating aspects of treating psoriasis is the tendency of psoriatic skin lesions to recur after therapy has been discontinued. Since the cause is complicated and is usually related to genetics, infection, immunity, and endocrine. Some cases are even incurable. Therefore, IGFL1 might be a potential candidate target for psoriasis treatment [3, 8].
More reports suggested that IGFL1 participates in regulations of multiple tumors. Current studies about associations between IGFL1 and tumors include Basal-like breast cancer (which is one type of triple negative breast cancer), ovarian cancer, liver cancer, melanoma, and esophageal squamous cancer.
In Basal-like breast cancer, IGFL2-AS1 was found to promote tumor cell proliferation and growth by regulating IGFL1 (Figure 1) [1]. In addition, IGFL1 and IGFL2-AS1 have been identified as oncogenes via in vivo and in vitro experiments. Analysis of clinical samples showed that IGFL1 was overexpressed in triple-negative breast cancer patients [1]. In ovarian cancer, high expression of IGFL1 was closely associated with poor prognosis by TCGA database analysis. And IGFL1 may be a potential predictor of ovarian cancer [9]. In liver cancer, TCGA data also identified several tumor-associated fibroblasts (CAF) marker targets such as IGFL1. [10] In melanoma, analysis of differentially expressed genes (DEGs) denoted that changes in IGFL1 expression levels could affect tolerance [11]. In esophageal squamous carcinoma, IGFL1 was considered as a target gene for differentially expressed lncRNAs [12].
Figure 1. IGFL1 is involved in regulating Basal-like breast cancer
At present, it remains to be explored that the effectiveness of IGFL1 targets in the clinical applications. However, with further deep understanding of the IGFL1 mechanisms, the role of IGFL1 in various biological networks is expected to provide new insights for the diagnosis and treatment of many diseases. In fact, an increasing number of biological analyses have shown that IGFL1 plays an essential role in growth, inflammatory diseases, and tumorigenesis, which predicts that IGFL1 is one of the potential drugs for inflammatory skin diseases (allergic skin diseases and psoriasis) and oncological diseases (breast and ovarian cancers).
To fully serve the researchers and pharmaceutical companies in their research on the IGFL1, CUSABIO offers active protein products IGFL1 (Code:CSB-MP764932HU) and its receptor IGFLR1 (Code: CSB-MP862025HUd9) to assist your research on the mechanisms of IGFL1 or its potential in clinical applications.
● Recombinant Human Insulin growth factor-like family member 1(IGFL1) (Active)
Purity was greater than 95% as determined by SDS-PAGE.(Tris-Glycine gel) Discontinuous SDS-PAGE (reduced) with 5% enrichment gel and 15% separation gel.
Measured by its binding ability in a functional ELISA. Immobilized Human IGFLR1 (CSB-MP862025HU) at 2 μg/ml can bind Human IGFL1, the EC50 is 32.33-47.52 ng/mL.
● Recombinant Human IGF-like family receptor 1(IGFLR1), partial (Active)
Purity was greater than 95% as determined by SDS-PAGE.(Tris-Glycine gel) Discontinuous SDS-PAGE (reduced) with 5% enrichment gel and 15% separation gel.
Measured by its binding ability in a functional ELISA. Immobilized Human IGFLR1 at 2 μg/ml can bind Human IGFL1 (CSB-MP764932HUh8), the EC50 is 4.640- 5.722 ng/mL.
References
[1] Wang, Haixia, et al. "KLF5-induced lncRNA IGFL2-AS1 promotes basal-like breast cancer cell growth and survival by upregulating the expression of IGFL1." Cancer Letters (2021).
[2] Emtage, Peter, et al. "IGFL: a secreted family with conserved cysteine residues and similarities to the IGF superfamily." Genomics 88.4 (2006): 513-520.
[3] Lobito, Adrian A., et al. "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." Journal of Biological Chemistry 286.21 (2011): 18969-18981.
[4] Yu, Yao, et al. "A whole-exome case-control association study to characterize the contribution of rare coding variation to pancreatic cancer risk." Human Genetics and Genomics Advances 3.1 (2022): 100078.
[5] Zhang, Lei, et al. "Lineage tracking reveals dynamic relationships of T cells in colorectal cancer." nature 564.7735 (2018): 268-272.
[6] Jin, Lei, Lin Deng, and Wanchun Wang. "Candidate Genes of Allergic Dermatitis Are Associated with Immune Response." Journal of Healthcare Engineering 2022 (2022).
[7] Lobito, Adrian A., et al. "MURINE IGFL AND HUMAN IGFL1 ARE INDUCED IN INFLAMMATORY SKIN CONDITIONS AND BIND TO A NOVEL TNF RECEPTOR FAMILY MEMBER, IGFLR1." (2011).
[8] Guo, Pi, et al. "Gene expression profile based classification models of psoriasis." Genomics 103.1 (2014): 48-55.
[9] Ji, Xiaorong, et al. "High Expression of IGFL1 Predicts Poor Prognosis of Serous Ovarian Carcinoma." revista Argentina de Clínica Psicológica 29.4 ( 2020): 981-989.
[10] Zou, Baojia, et al. "A novel 12-marker panel of cancer-associated fibroblasts involved in progression of hepatocellular carcinoma." Cancer management and research 10 (2018): 5303.
[11] Shi, Alvin, et al. "Plasma-derived extracellular vesicle analysis and deconvolution enable prediction and tracking of melanoma checkpoint blockade outcome." Science advances 6.46 (2020): eabb3461.
[12] Kodaira, Himiko, et al. "ANXA10 induction by interaction with tumor-associated macrophages promotes the growth of esophageal squamous cell carcinoma." Pathology international 69.3 (2019): 135-147.
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