LAMP2

Official Full Name

lysosomal associated membrane protein 2

Organism

Homo sapiens

GeneID

3920

Background

The protein encoded by this gene is a member of a family of membrane glycoproteins. This glycoprotein provides selectins with carbohydrate ligands. It may play a role in tumor cell metastasis. It may also function in the protection, maintenance, and adhesion of the lysosome. Alternative splicing of this gene results in multiple transcript variants encoding distinct proteins. [provided by RefSeq, Jul 2008]

Synonyms

DND; LAMPB; CD107b; LAMP-2; LGP-96; LGP110;

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Detailed Information

Recent Progress

Following the degradative pathway, vesicles loaded with extracellular material, eventually dock and fuse with lysosomes, acquiring specific membrane markers of these organelles and acid hydrolases responsible for digesting their content. The lysosomal-associated membrane protein 2 (LAMP-2), is found in late stages of endosome maturation and may be used as a marker of lysosome-associated membranes. In addition to the expression on the lysosomal membrane, LAMP2 has also been found relocalizing to the cell surface of some highly metastatic tumor cells.

Lamp2 and SACC

Salivary Adenoid Cystic Carcinoma (SACC) is a tumor characterized by inevitable local progression and terminal hematogenous metastasis. In one research, high expression of LC3, LAMP2 and NRF2 were found in SACC patients, and LC3, LAMP2 and NRF2 expression were significantly higher in SACC than as compared with pleomorphic adenoma and normal salivary gland. Moreover, the high expression of KEAP1 had significant correlations with LC3, LAMP2 and NRF2. These findings demonstrated that up-regulation of LC3, LAMP2 and NRF2 were associated with carcinogenesis and progression of SACC patients, suggesting that they may be useful molecular targets in salivary adenoid cystic carcinoma.

Lamp2 and LSD

Lysosomal storage disorders (LSDs) are described by the absence or deficiency in hydrolase activity leading to substrate accumulation within lysosomal components and to the onset of several diseases. It is known that lymphocytes infected by Epstein–Barr virus (EBV) are able to form cytoplasmic vacuoles, which work as a storage compartment for lysosomal acidic hydrolases. In one study, researchers validated the EBV as a transforming agent of B lymphocytes in stability studies of long-term stored samples.

Lamp2 and ESCC

To detect the expression levels of LAMP2 and its roles in esophageal squamous cell carcinoma (ESCC), six hundred and ten tissue samples of ESCC were collected. The LAMP2 expression levels were significantly different based on degrees of histological differentiation. The similar results were also observed in TNM stages. LAMP2 expression levels negatively correlated with degrees of histological differentiation. Regression analysis showed that the LAMP2 expression levels were correlated with the degrees of histological differentiation and TNM stages. Besides, Kaplan survival curves indicated that patients with higher expression of LAMP2 exhibited poor prognosis. These findings demonstrated that LAMP2 expression levels correlated with tumor histological differentiation and TNM stages, and high expression of LAMP2 predicts poor prognosis in patients with ESCC.

Lamp2 and PCa

Neuroendocrine (NE) prostate cancer (PCa) is a highly aggressive subtype of prostate cancer associated with resistance to androgen ablation therapy. Using LNCaP prostate cancer cells cultured in a serum-free medium for 6 days, researchers identified up-regulation of 155 genes, among them is LAMP2. Then the up-regulation of LAMP2 was confirmed in NE cells. Further analysis showed that mRNA up-regulation correlated with increased levels of LAMP2 protein. On the one hand, it was revealed that AKT inhibitor IV as well as Beclin1 and Atg5 knockdown attenuated LAMP2 expression in NE cells. On the other hand, LAMP2 knockdown by siRNA led to a marked blockage of autophagy, prevention of NE differentiation and decrease of cell survival. Taken together, these findings suggested that LAMP2 overexpression can assist NE differentiation of LNCaP cells. LAMP2 could thus be a potential biomarker and potential target for NE prostate cancer (Fig.1).

Fig. 1. Lysosomal-associated membrane protein 2 (LAMP2) is over-expressed in neuroendocrine differentiated LNCaP cells. (Cecilia et al, 2016)

Lamp2 and Danon Disease

Danon disease is an X-linked disorder with the clinical triad of cardiomyopathy, skeletal myopathy, and mental retardation. Early diagnosis of this disease remains a challenge, especially in the pediatric population. In one study, researchers developed a targeted panel-based next generation sequencing pipeline to identify mutations in about 130 pediatric patients with either hypertrophic cardiomyopathy (HC) or idiopathic dilated cardiomyopathy (IDC). This led to the identification of LAMP2 mutations in 4 of the 65 probands with HC, including 3 novel nonsense mutations. No LAMP2 mutation was detected in the other 72 probands with IDC. Results also revealed absent LAMP2 expression in both cardiac and skeletal muscle samples of the first proband and severely decreased LAMP2 expression in the skeletal muscle samples of the second proband. In conclusion, cardiomyopathy in the patients with Danon disease may occur during early childhood and tend to be HC rather than IDC in both affected men and women. The inclusion of LAMP2 gene in cardiomyopathy genetic screening panels may contribute to early diagnosis of Danon disease.

References:

Huang, C. F., Deng, W. W., Zhang, L., Zhang, W. F., & Sun, Z. J. (2016). Expression of lc3, lamp2, keap1 and nrf2 in salivary adenoid cystic carcinoma. Pathology & Oncology Research, 22(1), 109-114.
Mello, A. S., Goldim, M. P., Mezzalira, J., Garcia, C. S., Daitz, V. V., & Castilhos, C. D., et al. (2014). Lamp2 as a marker of ebv-mediated b lymphocyte transformation in the study of lysosomal storage diseases. Molecular & Cellular Biochemistry, 385(1-2), 1-6.
Li, L., Wang, W., Zhang, R., Liu, J., Yu, J., & Wu, X., et al. (2017). High expression of lamp2 predicts poor prognosis in patients with esophageal squamous cell carcinoma. Cancer Biomarkers, 19(3), 305.
Cecilia, M., Alicia, B., Diana, V. C., Ágata, R. T., Manuel, A. D., & Inés, D. L., et al. (2016). Up-regulated expression of lamp2 and autophagy activity during neuroendocrine differentiation of prostate cancer lncap cells:. Plos One, 11(9), e0162977.
Fu, L., Luo, S., Cai, S., Hong, W., Guo, Y., & Wu, J., et al. (2016). Identification of lamp2 mutations in early-onset danon disease with hypertrophic cardiomyopathy by targeted next-generation sequencing. American Journal of Cardiology, 118(6), 888-894.
Bao, L., Lv, L., Feng, J., Chen, Y., Wang, X., & Han, S., et al. (2016). Mir-487b-5p regulates temozolomide resistance of lung cancer cells through lamp2-medicated autophagy. Dna & Cell Biology, 35(8), 385.

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