Background: Autophagocytosis is a biological process involving the controlled distribution of cell fragments and organelles in order to obtain an additional source of energy. LAMP3 (lysosome-associated membrane protein 3) is a heavily glycosylated integral membrane protein located mainly in the lysosomal membrane. Recent studies have shown that it participates in tumor metastasis and drug resistance. Its main role is contribution to tumor cells proliferation, migration and invasion. The aim of this study was to determine changes in transcriptional activity of LAMP3 at various stages of colorectal cancer. In addition, an attempt was made to select miRNAs potentially regulating LAMP3 expression using bioinformatic databases. Methods: The study was conducted on healthy colon samples and colon cancer samples in four stages. Molecular analysis included the extraction of total RNA, purification of the obtained extracts, expression profile analysis using oligonucleotide microarray technique and in silico determination of miRNAs potentially regulating the LAMP3 expression. Results: The level of LAMP3 expression is higher in colorectal adenocarcinoma cells than in non-cancerous cells and depends on the stage of the disease. Conclusions: LAMP3 may promote cancer progression, metastasis and cause the resistance to treatment.
Grützkau, A., Smorodchenko, A., Lippert, U., et al. (2004) LAMP-1 and LAMP-2, But Not LAMP-3, Are Reliable Markers for Activation-Induced Secretion of Human Mast Cells. Cytometry, 61A, 62-68. https://doi.org/10.1002/cyto.a.20068
Liao, X., Chen, Y., Liu, D., et al. (20115) High Expression of LAMP3 Is a Novel Biomarker of Poor Prognosis in Patients with Esophageal Squamous Cell Carcinoma. International Journal of Molecular Sciences, 16, 17655-17667.
Dominguez-Bautista, J.A., Klinkenberg, M., Brehm, N., et al. (2015) Loss of Lysosome-Associated Membrane Protein 3 (LAMP3) Enhances Cellular Vulnerability against Proteasomal Inhibition. European Journal of Cell Biology, 94, 148-161.
Sun, R., Wang, X., Zhu, H., et al. (2014) Prognostic Value of LAMP3 and TP53 Overexpression in Benign and Malignant Gastrointestinal Tissues. Oncotarget, 5, 12398-12409. https://doi.org/10.18632/oncotarget.2643
Nagelkerke, A., Bussink, J., Mujcic, H., et al. (2013) Hypoxia Stimulates Migration of Breast Cancer Cells via the PERK/ATF4/LAMP3-Arm of the Unfolded Protein Response. Breast Cancer Research, 15, R2. https://doi.org/10.1186/bcr3373
Mujcic, H., Nagelkerke, A., Rouschop, K.M., et al. (2013) Hypoxic Activation of the PERK/eIF2a Arm of the Unfolded Protein Response Promotes Metastasis through Induction of LAMP3. Clinical Cancer Research, 19, 6126-6137.
B’chir, W., Maurin, A.C., Carraro, V., et al. (2013) The eIF2a/ATF4 Pathway Is Essential for Stress Induced Autophagy Gene expression. Nucleic Acids Research, 41,7683-7699. https://doi.org/10.1093/nar/gkt563
Blázquez, A.B., Escribano-Romero, E., Merino-Ramos, T., et al. (2014) Stress Responses in Flavivirus-Infected Cells Activation of Unfolded Protein Response and Autophagy. Frontiers in Microbiology, 5, 266.
Ozaki, K., Nagata, M., Suzuki, M., et al. (1998) Isolation and Characterization of a Novel Human Lung-Specific Gene Homologous to Lysosomal Membrane Glycoproteins 1 and 2: Significantly Increased Expression in Cancers of Various Tissues. Cancer Research, 58, 3499-3503.
Kania, E., Pajak, B. and Orzechowski, A. (2015) Calcium Homeostasis and ER Stress in Control of Autophagy in Cancer Cells. Biomed Research International, 2015, Article ID: 352794. https://doi.org/10.1155/2015/352794
Burada, F., Nicoli, E.R., Ciurea, M.E., et al. (2015) Autophagy in Colorectal Cancer: An Important Switch from Physiology to Pathology. World Journal of Gastrointestinal Oncology, 7, 271-284. https://doi.org/10.4251/wjgo.v7.i11.271
Eskelinen, E.L. and Saftig, P. (2009) Autophagy: A Lysosomal Degradation Pathway with a Central Role in Health and Disease. BiochimBiophysActa, 1793, 664-673.
Wilke, S., Krausze, J. and Büssow, K. (2012) Crystal Structure of the Conserved Domain of the DC Lysosomal Associated Membrane Protein Implications for the Lysosomalglycocalyx. BMC Biology, 10, 62.
Nagelkerke, A., Sieuwerts, A.M., Bussink, J., et al. (2014) LAMP3 Is Involved in Tamoxifen Resistance in Breast Cancer Cells through the Modulation of Autophagy. Endocrine-Related Cancer, 21, 101-112. https://doi.org/10.1530/ERC-13-0183
Arensdorf, A.M., Diedrichs, D. and Rutkowski, D.T. (2013) Regulation of the Transcriptome by ER Stress Non-Canonical Mechanisms and Physiological Consequences. Frontiers in Genetics, 4, 256. https://doi.org/10.3389/fgene.2013.00256
Parcheta, P. and Klujszo, E.H. (2014) Recurrent Erythema Nodosum and Pulmonary Lymph Node Tuberculosis in a Patient Treated for Psoriatic. Dermatology Review, 101, 390-396. https://doi.org/10.5114/dr.2014.46069
De Simone, C., Caldarola, G., Maiorino, A., et al. (2016) Clinical Predictors of Nonresponse to Anti-TNF-a Agents in Psoriatic Patients: A Retrospective Study. Dermatology and Therapy, 29, 372-376. https://doi.org/10.1111/dth.12364
Kheirelseid, E.A.H., Miller, N. and Kerin, M.J. (2013) Molecular Biology of Colorectal Cancer: Review of the Literature. American Journal of Physiology, 3, 72-80.
Grande-Pulido, E., Riquelme-Oliveia, A., Ballesteros-Bargues, J., et al. (2011) Molecular Biology of Colorectal Cancer. In: Cidón, E.U., Ed., The Challenge of Colorectal Cancer: A Review Book, Research Signpost, Kerala, India, 35-51.