Increased LAMP2A levels correlate with a shorter disease-free survival of HER2 negative breast cancer patients and increased breast cancer cell viability

Igor Tokarchuk; Félice A Janser; Anna M Schläfli; Marta Teixeira Pinto; Magali Humbert; Nicolas J Niklaus; Sabina Berezowska; Rupert Langer; Mario P Tschan

doi:10.1016/j.bbrc.2021.06.082

Increased LAMP2A levels correlate with a shorter disease-free survival of HER2 negative breast cancer patients and increased breast cancer cell viability

Biochem Biophys Res Commun. 2021 Sep 10:569:47-53. doi: 10.1016/j.bbrc.2021.06.082. Epub 2021 Jul 3.

Authors

Igor Tokarchuk¹, Félice A Janser¹, Anna M Schläfli², Marta Teixeira Pinto³, Magali Humbert⁴, Nicolas J Niklaus¹, Sabina Berezowska², Rupert Langer⁵, Mario P Tschan⁶

Affiliations

¹ Institute of Pathology, University of Bern, Bern, Switzerland; Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland.
² Institute of Pathology, University of Bern, Bern, Switzerland.
³ Ipatimup - Institute of Molecular Pathology and Immunology of the University of Porto, Rua Júlio Amaral de Carvalho, 45, 4200-135, Porto, Portugal.
⁴ Institute of Pathology, University of Bern, Bern, Switzerland; TRANSAUTOPHAGY: European Network for Multidisciplinary Research and Translation of Autophagy Knowledge, COST Action, CA15138, Spain.
⁵ Institute of Pathology, University of Bern, Bern, Switzerland; Institute of Pathology, Kepler University Hospital and Johannes Kepler University Linz, Linz, Austria. Electronic address: rupert.langer@kepleruniklinikum.at.
⁶ Institute of Pathology, University of Bern, Bern, Switzerland; TRANSAUTOPHAGY: European Network for Multidisciplinary Research and Translation of Autophagy Knowledge, COST Action, CA15138, Spain. Electronic address: mario.tschan@pathology.unibe.ch.

PMID: 34229122
DOI: 10.1016/j.bbrc.2021.06.082

Abstract

Chaperone Mediated Autophagy (CMA) is a selective autophagy pathway deregulated in many cancers. In this study, we were aiming at understanding the importance of CMA in breast cancer. To this end, we examined the expression of the CMA markers HSP8 and LAMP2A in different breast cancer cell lines and found a wide range of LAMP2A expression levels across the cell lines analyzed. Next, we applied a specific immunohistochemical staining protocol to a tissue microarray derived from a cohort of 365 breast cancer patients. Therefore, we were able to find a correlation of high LAMP2A but not HSPA8 (HSC70) with worse disease free survival in patients with HER2 negative tumors (p = 0.026) which was independent prognostic parameter from pT category, pN category and grading in a multivariate model (HR = 1.889; 95% CI = 1.039-3.421; p = 0.037). In line, low LAMP2A levels decrease proliferation of the breast cancer cell lines T47D and MCF-7 in vitro. Our data suggest that LAMP2A supports a more severe breast cancer cell phenotype.

Keywords: Breast cancer; CMA; Chaperone mediated autophagy; HSC70; HSP8; LAMP2A.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Aged, 80 and over
Blotting, Western
Breast Neoplasms / genetics
Breast Neoplasms / metabolism*
Breast Neoplasms / therapy
Cell Culture Techniques / methods*
Cell Line, Tumor
Cell Proliferation / genetics
Cell Survival / genetics
Chaperone-Mediated Autophagy / genetics
Disease-Free Survival
Female
Humans
Lysosomal-Associated Membrane Protein 2 / genetics
Lysosomal-Associated Membrane Protein 2 / metabolism*
MCF-7 Cells
Middle Aged
RNA Interference
Receptor, ErbB-2 / metabolism*

Substances

LAMP2 protein, human
Lysosomal-Associated Membrane Protein 2
ERBB2 protein, human
Receptor, ErbB-2