ECM1

Official Full Name

extracellular matrix protein 1

Organism

Homo sapiens

GeneID

1893

Background

This gene encodes a soluble protein that is involved in endochondral bone formation, angiogenesis, and tumor biology. It also interacts with a variety of extracellular and structural proteins, contributing to the maintenance of skin integrity and homeostasis. Mutations in this gene are associated with lipoid proteinosis disorder (also known as hyalinosis cutis et mucosae or Urbach-Wiethe disease) that is characterized by generalized thickening of skin, mucosae and certain viscera. Alternatively spliced transcript variants encoding distinct isoforms have been described for this gene. [provided by RefSeq, Feb 2011]

Synonyms

URBWD;

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Detailed Information

Extracellular matrix protein 1 (ECM1) is a research hotspot in the field of oncology in recent years, and plays an important role in the development of malignant epithelial tumors. There are four kinds of mRNA and encoded proteins of ECM1 gene: (1) ECM1a is 1800 bp, including full-length mRNA of all exons, and encodes a protein of 540 amino acids. ECM1a protein is widely expressed in a variety of tissues and tissues, including skin, skeletal muscle, lung, liver, pancreas, small intestine, kidney, prostate, ovary, testis, etc., and most of the placenta and heart. (2)ECM1b is 1 400 bp, lacking the shorter mRNA of exon 7, and encodes a protein of 415 amino acids, which is restricted to tonsils and keratinocytes. (3) ECM1c, whose gene sequence contains full-length mRNA of all exons, and adds an exon 5a homologous to the sixth exon of the murine ECM1 gene in the 5th intron region. The encoded protein is expressed only in the basal layer of the human epidermis. (4) ECM1d, which encodes only 57 amino acids, its function is unclear.

ECM1 Function

The study found that ECM1 may be involved in angiogenesis by stimulating chicken chorioallantoic vesicles by human recombinant ECM1 and vascular formation in the chorioallantoic vesicle. ECM1 inhibits chondrocyte hypertrophy, cartilage matrix mineralization, and cartilage bone formation, and is a negative regulator of cartilage formation. ECM1 is also involved in keratinocyte differentiation. In addition, studies have found that high levels of ECM1 autoantibodies are present in the serum of patients with sclerosing moss, and therefore ECM1 is considered to be closely related to humoral immunity in patients with sclerosing moss.

In the study of patients with lipoproteinosis, the 6th and 7th exons of the ECM1 gene in this patient have functional defects. This can cause lymphangiogenesis between the skin and mucous membranes, causing local deposition of lipids and proteins, resulting in lesions of the lipoproteinosis. In recent years, according to most related studies on ECM1, ECM1 is highly expressed in malignant tumors and is associated with invasion and metastasis of malignant tumors. It can be seen that ECM1 is involved in a variety of biological processes, including embryonic cartilage formation, angiogenesis, cell proliferation, skin differentiation, and tumorigenesis, which is of great significance in the occurrence of malignant epithelial tumors.

The Warburg effect is an oncogenic metabolic switch that allows cancer cells to take up more glucose than normal cells and contribute to anaerobic glycolysis. Lee et al. found that EGF-dependent ERK activation regulated by ECM1 not only induced PKM2 phosphorylation but also induced gene expression of GLUT1 and LDHA. These findings provide evidence that ECM1 plays an important role in promoting the PKM2-mediated Warburg effect.

ECM1 plays a key role in the structure and homeostatic biology of the skin, particularly in the proliferation and differentiation of epidermal keratinocytes, the remodeling of the basement membrane, angiogenesis, malignant transformation, and aging. The study found that ECM1, as a binding core and/or scaffold protein, not only produces a wide range of differentiation properties for epidermal keratinocytes but also acquires immune tolerance and allergic responses through specific T cell subsets.

ECM1 Figure 1. Summary of the different binding partners of ECM1 in the dermal-epidermal junction. (Oyama, et al. 2017)

ECM1 and Tumor

Recent studies have shown that ECM1 is highly expressed in malignant epithelial tumors such as breast cancer, esophageal cancer, gastric cancer, liver cancer, cholangiocarcinoma, colorectal cancer, laryngeal cancer, thyroid cancer, lung cancer, and melanoma. And ECM1 is closely related to the occurrence, development, metastasis, and invasion of malignant epithelial tumors.

In a study of the effects of ECM1 expression levels on breast cancer prognosis, the Cox regression model was used to analyze the association between ECM1 expression and survival in 134 patients with invasive breast cancer. The results indicate that ECM1 can be used as an important predictor of prognosis in breast cancer patients. In addition, the study found that ECM1 can be used as a diagnostic marker for malignant thyroid nodules, and also as a marker for the extent of differentiated thyroid cancer. Ye et al. found that overexpression of miR-486-3p inhibits cell growth and metastasis by targeting ECM1. Lal et al. also found that ECM1 expression can be used as an independent diagnostic indicator for thyroid cancer, and found that real-time quantitative RT-PCR detection method is more sensitive than immunohistochemistry.

One study found that ECM1 expression was significantly elevated in lung cancer tissues with positive lymph node metastasis compared with lung cancer tissues with lymph node metastasis, suggesting that ECM1 is associated with lymph node metastasis in lung cancer. Studies have examined lung acinar soft tissue sarcoma and similarly found that ECM1 expression levels are significantly higher than normal lung tissue. Thus, the increased expression level of ECM1 is involved in the development, invasion, and metastasis of lung tumors.

Lal et al. detected a variety of melanoma cell lines and found that ECM1 protein was overexpressed in melanoma cells compared with normal melanocytes, and knocking out ECM1 resulted in decreased invasiveness of melanoma cells. This suggests that ECM1 may be involved in the occurrence and invasion of melanoma. At the same time, Lal et al. also found that the expression of ECM1 in pigmentoma cells may be regulated by TPAP2C.

References:

Uematsu, S., Goto, Y., Suzuki, T., Sasazawa, Y., Dohmae, N., & Simizu, S. (2016). N-glycosylation of extracellular matrix protein 1 (ecm1) regulates its secretion, which is unrelated to lipoid proteinosis. Febs Open Bio, 4(1), 879-885.
Lee, K. M., Nam, K., Oh, S., Lim, J., Lee, T., & Shin, I. (2015). Ecm1 promotes the warburg effect through egf-mediated activation of pkm2. Cellular Signalling, 27(2), 228-235.
Oyama, N., & Merregaert, J. (2017). The extracellular matrix protein 1 (ecm1) in molecular-based skin biology.
Lal, G., Contreras, P. G., Kulak, M., Woodfield, G., Bair, T., & Domann, F. E., et al. (2013). Human melanoma cells over-express extracellular matrix 1 (ecm1) which is regulated by tfap2c. Plos One, 8(9), e73953.
Ye, H., Yu, X., Xia, J., Tang, X., Tang, L., & Chen, F. (2016). Mir-486-3p targeting ecm1 represses cell proliferation and metastasis in cervical cancer. Biomedicine & Pharmacotherapy, 80, 109-114.

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