liu.seSearch for publications in DiVA
Change search
Link to record
Permanent link

Direct link
BETA
Johansson, Ann-Charlotte
Alternative names
Publications (10 of 19) Show all publications
Jedlinski, A., Garvin, S., Johansson, A.-C., Edqvist, P.-H., Pontén, F. & Roberg, K. (2017). Cetuximab sensitivity of head and neck squamous cell carcinoma xenografts is associated with treatment-induced reduction of EGFR, pEGFR, and pSrc. Journal of Oral Pathology & Medicine (9), 717-724
Open this publication in new window or tab >>Cetuximab sensitivity of head and neck squamous cell carcinoma xenografts is associated with treatment-induced reduction of EGFR, pEGFR, and pSrc
Show others...
2017 (English)In: Journal of Oral Pathology & Medicine, ISSN 0904-2512, E-ISSN 1600-0714, no 9, p. 717-724Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: The aim of this study was to validate in vitro drug sensitivity testing of head and neck squamous cell carcinoma (HNSCC)cell lines in an in vivo xenograft model, and to identify treatment-induced changes in the EGFR signaling pathway that could be used as markersfor cetuximab treatment response.

METHODS: The in vitro cetuximab sensitivity of two HNSCC cell lines, UT-SCC-14 and UTSCC-45, was assessed using a crystal violet assay. In order to determine the corresponding in vivo sensitivity, UT-SCC-14 and UT-SCC-45 xenografts were generated in female BALB/c (nu/nu) nude mice. Mice were given three injections of intraperitoneal cetuximab or PBS and the tumor volume was recorded continuously. The expression of epidermal growth factor receptor (EGFR), phosphorylated EGFR (pEGFR), phosphorylated Src (pSrc), and Ki67 was investigated by immunohistochemistry.

RESULTS: The treatment sensitive UT-SCC-14 cells were found to have an intrinsic cetuximab sensitivity (ICmabS) of 0.15 whereas the ICmabS of the insensitive cell line UT-SCC-45 was 0.78. The corresponding size ratio between untreated and cetuximab treated xenografts was 0.22 and 0.83 for UT-SCC-14 and UT-SCC-45, respectively. UT-SCC-14 cells had a higher baseline expression of pEGFR as compared to UT-SCC-45. Furthermore, in UT-SCC-14 xenografts there was a decrease in EGFR, pEGFR and pSrc upon cetuximab treatment. In contrast, a slight cetuximab-induced increase in EGFR, pEGFR and pSrc was observed in treatment-resistant UT-SCC-45 xenografts.

CONCLUSIONS: The in vitro treatment sensitivity was reproduced in the in vivo model and cetuximab sensitivity was found to associate with a treatment-induced reduction in pEGFR and pSrc.

Place, publisher, year, edition, pages
John Wiley & Sons, 2017
National Category
Medical and Health Sciences Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-113742 (URN)10.1111/jop.12545 (DOI)000412303500009 ()28036101 (PubMedID)
Note

Funding agencies: Foundation of Ake Wiberg; County Council of Ostergotland; Research Funds of Linkoping University Hospital; Cancer Foundation of Ostergotland; Foundation of Magn. Bergvall; The Swedish Cancer Society [2010/545]

The previous status of this publication was Manuscript

Available from: 2015-01-29 Created: 2015-01-29 Last updated: 2018-05-03Bibliographically approved
Ansell, A., Jedlinski, A., Johansson, A.-C. & Roberg, K. (2016). Epidermal growth factor is a biomarker for poor cetuximab response in tongue cancer cells. Journal of Oral Pathology & Medicine, 45(1), 9-16
Open this publication in new window or tab >>Epidermal growth factor is a biomarker for poor cetuximab response in tongue cancer cells
2016 (English)In: Journal of Oral Pathology & Medicine, ISSN 0904-2512, E-ISSN 1600-0714, Vol. 45, no 1, p. 9-16Article in journal (Refereed) Published
Abstract [en]

Background: Epidermal growth factor receptor (EGFR) is a target for treatment in tongue cancer. Here, EGFR ligands were evaluated for their potential uses as predictive biomarkers of cetuximab treatment response.

Methods: In three tongue cancer cell lines the influences of epidermal growth factor (EGF), amphiregulin (AR), and epiregulin (EPR) on tumour cell proliferation and cetuximab response were evaluated by the addition of recombinant human (rh) proteins or the siRNA-mediated downregulation of endogenous ligand production.

Results: EGF or AR downregulation suppressed the proliferation of all investigated cell lines. Furthermore, all cell lines displayed increased cetuximab resistance upon the addition of rhEGF, whereas EGF silencing resulted in an improved cetuximab response in one cell line.

Conclusions: Our data suggest that EGF and AR are critical components of the EGFR signalling network required for full proliferative potential. Moreover, EGF is a potential predictive biomarker of poor cetuximab response and a possible treatment target.

Place, publisher, year, edition, pages
Wiley-Blackwell, 2016
Keywords
Head and neck cancer; Tongue cancer; Erbitux; EGFR ligands; treatment response
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:liu:diva-100675 (URN)10.1111/jop.12310 (DOI)000369990100003 ()
Note

Funding agencies: Foundation of Ake Wiberg; Swedish Cancer Society [2008/552, 2010/545]; County Council of Ostergotland; Linkoping University Hospital; Foundation of Magnus Bergvall; Cancer Foundation of Ostergotland

Vid tiden för disputation förelåg publikationen endast som manuskript

Available from: 2013-11-11 Created: 2013-11-11 Last updated: 2017-05-03
Jerhammar, F., Johansson, A.-C., Ceder, R., Welander, J., Jansson, A., Grafstrom, R. C., . . . Roberg, K. (2014). YAP1 is a potential biomarker for cetuximab resistance in head and neck cancer. Oral Oncology, 50(9), 832-839
Open this publication in new window or tab >>YAP1 is a potential biomarker for cetuximab resistance in head and neck cancer
Show others...
2014 (English)In: Oral Oncology, ISSN 1368-8375, E-ISSN 1879-0593, Vol. 50, no 9, p. 832-839Article in journal (Refereed) Published
Abstract [en]

Objectives: Targeted therapy against the epidermal growth factor receptor (EGFR) only variably represents a therapeutic advance in head and neck squamous cell carcinoma (HNSCC). This study addresses the need of biomarkers of treatment response to the EGFR-targeting antibody cetuximab (Erbitux (R)). Materials and Methods: The intrinsic cetuximab sensitivity of HNSCC cell lines was assessed by a crystal violet assay. Gene copy number analysis of five resistant and five sensitive cell lines was performed using the Affymetrix SNP 6.0 platform. Quantitative real-time PCR was used for verification of selected copy number alterations and assessment of mRNA expression. The functional importance of the findings on the gene and mRNA level was investigated employing siRNA technology. The data was statistically evaluated using Mann-Whitney U-test and Spearmans correlation test. Results: Analysis of the intrinsic cetuximab sensitivity of 32 HNSCC cell lines characterized five and nine lines as cetuximab sensitive or resistant, respectively. Gene copy number analysis of five resistant versus five sensitive cell lines identified 39 amplified protein-coding genes, including YAP1, in the genomic regions 11q22.1 or 5p13-15. Assessment using qPCR verified that YAP1 amplification associated with cetuximab resistance. Amplification of YAP1 correlated to higher mRNA levels, and RNA knockdown resulted in increased cetuximab sensitivity. Assessment of several independent clinical data sets in the public domain confirmed YAP1 amplifications in multiple tumor types including HNSCC, along with highly differential expression in a subset of HNSCC patients. Conclusion: Taken together, we provide evidence that YAP1 could represent a novel biomarker gene of cetuximab resistance in HNSCC cell lines.

Place, publisher, year, edition, pages
Elsevier, 2014
Keywords
Head and neck cancer; SCCHN; YAP1; Predictive marker; Treatment response; Gene copy number; Drug resistance
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-110268 (URN)10.1016/j.oraloncology.2014.06.003 (DOI)000340267300011 ()24993889 (PubMedID)
Note

Funding Agencies|Swedish Cancer Society [2008/552, 2010/545]; Ake Wiberg foundation; National board of health and welfare; Ostergotland county council; Foundation of Olle Engkvist; Swedish Cancer and Allergy Fund; Swedish Research Council; Swedish Fund for Research

Available from: 2014-09-05 Created: 2014-09-05 Last updated: 2017-12-05
Jedlinski, A., Ansell, A., Johansson, A.-C. & Roberg, K. (2013). EGFR status and EGFR ligand expression influence the treatment response of head and neck cancer cell lines. Journal of Oral Pathology & Medicine, 42(1), 26-36
Open this publication in new window or tab >>EGFR status and EGFR ligand expression influence the treatment response of head and neck cancer cell lines
2013 (English)In: Journal of Oral Pathology & Medicine, ISSN 0904-2512, E-ISSN 1600-0714, Vol. 42, no 1, p. 26-36Article in journal (Refereed) Published
Abstract [en]

Background: Combination treatment (chemoradiotherapy) is the standard treatment for locally advanced head and neck squamous cell carcinoma (HNSCC); however, treatment resistance and local recurrence are significant problems. A high level of epidermal growth factor receptor (EGFR) has been associated with a more aggressive phenotype as well as decreased responsiveness to radio- or chemotherapy. We examined the role of EGFR status and EGFR ligand expression for the treatment response. Methods: Intrinsic sensitivity to radiotherapy, cisplatin, and cetuximab treatments was investigated in 25 HNSCC cell lines. EGFR gene copy number, mRNA and protein expression, EGFR and Akt phosphorylation status, and mRNA expression of the EGFR ligands were analyzed using quantitative PCR and ELISA and assessed for their impact on treatment sensitivity. Results: Different treatment modalities yielded great diversity in outcome; of note, cetuximab treatment stimulated growth in one cell line. When treatments were combined primarily additive effects were observed. While radioresistance tended to be associated with a high level of phosphorylated EGFR (pEGFR; P = 0.09), cetuximab-resistant cells had low levels of pEGFR (P = 0.13). The three most cetuximab-sensitive cell lines had high EGFR gene copy numbers. Furthermore, cetuximab treatment response was significantly correlated with epiregulin mRNA expression (r = -0.408, P = 0.043). Cisplatin-resistant tumor cells expressed significantly lower levels of EGFR protein (P = 0.04) compared to cisplatin-sensitive cells and tended to have lower levels of phosphorylated Akt (pAkt; P = 0.13) and lower expression levels of amphiregulin (P = 0.18). Conclusions: Epidermal growth factor receptor status and ligand expression influence the treatment sensitivity of HNSCC cells and may be useful as predictive markers.

Place, publisher, year, edition, pages
John Wiley and Sons, 2013
Keywords
chemoradiotherapy, EGFR, epiregulin, Erbitux (R), HB-EGF, SCCHN, TGF-a, treatment response
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-87963 (URN)10.1111/j.1600-0714.2012.01177.x (DOI)000312998500004 ()
Note

Funding Agencies|Swedish Laryng Foundation||Foundation of Olle Engkvist, Building Contractor||Linkoping University Hospital||

Available from: 2013-01-28 Created: 2013-01-28 Last updated: 2017-12-06
Ansell, A., Kankainen, M., Jönsson, J.-I., Monni, O., Roberg, K. & Johansson, A.-C. (2013). Molecular cross-talk between head and neck squamous cell carcinoma cells and cancer-associated fibroblasts.
Open this publication in new window or tab >>Molecular cross-talk between head and neck squamous cell carcinoma cells and cancer-associated fibroblasts
Show others...
2013 (English)Manuscript (preprint) (Other academic)
Abstract [en]

Cancer-associated fibroblasts (CAFs) are one of the main components of the tumor stroma and are known to increase tumor growth and stimulate  invasion and metastasis. Increasing evidence suggests that CAFs may also be an important determinant of the response to various treatments. In this study we aimed to characterize the molecular cross-talk between CAFs and head and neck squamous cell carcinoma (HNSCC) cells.

HNSCC cell lines were co-cultured with their patient-matched CAFs for seven days, after which the gene expression of tumor cells was investigated by Affymetrix microarray. 58 protein coding genes were found to be differentially expressed (Q≤0.05) in tumor cells cocultured with CAFs when compared to tumor cells cultured alone. The top functions of these genes were cancer, cellular movement, and embryonic development as analyzed by Ingenuity Pathway Analysis. Nine genes were upregulated by ≥1.5-fold while the expression of 35 genes was found to be reduced by ≤ 0.67-fold. Several of the differentially expressed genes have been associated with epithelial-to-mesenchymal transition (EMT). The change in the expression of POSTN, GREM1, COL1A2, VIM, and MMP7 was verified by qPCR analysis. Moreover, the influence of CAFs on the proliferation, migration and cetuximab sensitivity of tumor cells was investigated, and was found to vary among the tumor cell-CAF pairs.

In conclusion, we demonstrate that CAF-derived signals cause changes in the expression of multiple genes, several of which are associated with an EMT phenotype of tumor cells. Furthermore, CAFs modulate the proliferation, migration and cetuximab treatment response of tumor cells.

Keywords
Head and neck cancer; Tongue cancer; Erbitux; EGFR ligands; treatment response
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-100678 (URN)
Available from: 2013-11-11 Created: 2013-11-11 Last updated: 2013-11-11Bibliographically approved
La Fleur, L., Johansson, A.-C. & Roberg, K. (2012). A CD44(high)/EGFR(low) Subpopulation within Head and Neck Cancer Cell Lines Shows an Epithelial-Mesenchymal Transition Phenotype and Resistance to Treatment. PLoS ONE, 7(9)
Open this publication in new window or tab >>A CD44(high)/EGFR(low) Subpopulation within Head and Neck Cancer Cell Lines Shows an Epithelial-Mesenchymal Transition Phenotype and Resistance to Treatment
2012 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, no 9Article in journal (Refereed) Published
Abstract [en]

Mortality in head and neck squamous cell carcinoma (HNSCC) is high due to emergence of therapy resistance which results in local and regional recurrences that may have their origin in resistant cancer stem cells (CSCs) or cells with an epithelial-mesenchymal transition (EMT) phenotype. In the present study, we investigate the possibility of using the cell surface expression of CD44 and epidermal growth factor receptor (EGFR), both of which have been used as stem cell markers, to identify subpopulations within HNSCC cell lines that differ with respect to phenotype and treatment sensitivity. Three subpopulations, consisting of CD44(high)/EGFR(low), CD44(high)/EGFR(high) and CD44(low) cells, respectively, were collected by fluorescence-activated cell sorting. The CD44(high)/EGFR(low) population showed a spindle-shaped EMT-like morphology, while the CD44(low) population was dominated by cobblestone-shaped cells. The CD44(high)/EGFR(low) population was enriched with cells in G0/G1 and showed a relatively low proliferation rate and a high plating efficiency. Using a real time PCR array, 27 genes, of which 14 were related to an EMT phenotype and two with stemness, were found to be differentially expressed in CD44(high)/EGFR(low) cells in comparison to CD44(low) cells. Moreover, CD44(high)/EGFR(low) cells showed a low sensitivity to radiation, cisplatin, cetuximab and gefitinib, and a high sensitivity to dasatinib relative to its CD44(high)/EGFR(high) and CD44(low) counterparts. In conclusion, our results show that the combination of CD44 (high) and EGFR (low) cell surface expression can be used to identify a treatment resistant subpopulation with an EMT phenotype in HNSCC cell lines.

Place, publisher, year, edition, pages
Public Library of Science, 2012
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-85609 (URN)10.1371/journal.pone.0044071 (DOI)000309556100010 ()
Note

Funding Agencies|Swedish Laryng Foundation||Foundation of Signhild Engkvist||Foundation of Ake Wiberg||Swedish Cancer Society|2008/5522010/545|County Council of Ostergotland||Linkoping University Hospital||

Available from: 2012-11-26 Created: 2012-11-26 Last updated: 2017-12-07
Johansson, A.-C., Ansell, A., Jerhammar, F., Bradic Lindh, M., Grenman, R., Munck-Wikland, E., . . . Roberg, K. (2012). Cancer-Associated Fibroblasts Induce Matrix Metalloproteinase-Mediated Cetuximab Resistance in Head and Neck Squamous Cell Carcinoma Cells. Molecular Cancer Research, 10(9), 1158-1168
Open this publication in new window or tab >>Cancer-Associated Fibroblasts Induce Matrix Metalloproteinase-Mediated Cetuximab Resistance in Head and Neck Squamous Cell Carcinoma Cells
Show others...
2012 (English)In: Molecular Cancer Research, ISSN 1541-7786, E-ISSN 1557-3125, Vol. 10, no 9, p. 1158-1168Article in journal (Refereed) Published
Abstract [en]

A growing body of evidence suggests that components of the tumor microenvironment, including cancer-associated fibroblasts (CAF), may modulate the treatment sensitivity of tumor cells. Here, we investigated the possible influence of CAFs on the sensitivity of head and neck squamous cell carcinoma (HNSCC) cell lines to cetuximab, an antagonistic epidermal growth factor receptor (EGFR) antibody. Cetuximab treatment caused a reduction in the proliferation rate of HNSCC cell lines, whereas the growth of HNSCC-derived CAF cultures was unaffected. When tumor cells were cocultured with CAFs in a transwell system, the cetuximab-induced growth inhibition was reduced, and a complete protection from growth inhibition was observed in one of the tumor cell lines investigated. Media that had been conditioned by CAFs offered protection from cetuximab treatment in a concentration-dependent manner, suggesting that the resistance to treatment was mediated by CAF-derived soluble factors. The coculture of HNSCC cell lines with CAFs resulted in an elevated expression of matrix metalloproteinase-1 (MMP-1) in both the tumor cells and CAFs. Moreover, the CAF-induced resistance was partly abolished by the presence of an MMP inhibitor. However, CAFs treated with siRNA targeting MMP-1 still protected tumor cells from cetuximab treatment, suggesting that several MMPs may cooperate to facilitate resistance or that the protective effect is mediated by another member of the MMP family. These results identify a novel CAF-dependent modulation of cetuximab sensitivity and suggest that inhibiting MMPs may improve the effects of EGFR-targeted therapy.

Place, publisher, year, edition, pages
American Association for Cancer Research, 2012
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-86135 (URN)10.1158/1541-7786.MCR-12-0030 (DOI)000310648300003 ()
Note

Funding Agencies|Johan and Jakob Soderberg Foundation||Foundation Olle Engqvist Byggmastare||Swedish Laryng Foundation||Borgholm Rotary Club||Swedish National Board of Health and Welfare||Lions Research Foundation||Lars Hierta Memorial Foundation||Tore Nilsson Foundation for Medical Research||Swedish Society for medical research||County Council of Ostergotland||Cancer Foundation of Ostergotland||Merck Serono||Swedish Research Council|349-2008-6578|Swedish Cancer Society|CAN 2009/1136CAN 2010/545|

Available from: 2012-12-07 Created: 2012-12-07 Last updated: 2017-12-07
Appelqvist, H., Johansson, A.-C., Linderoth, E., Johansson, U., Antonsson, B., Steinfeld, R., . . . Öllinger, K. (2012). Lysosome-Mediated Apoptosis is Associated with Cathepsin D-Specific Processing of Bid at Phe24,Trp48, and Phe183. Annals of Clinical and Laboratory Science, 42(3), 231-242
Open this publication in new window or tab >>Lysosome-Mediated Apoptosis is Associated with Cathepsin D-Specific Processing of Bid at Phe24,Trp48, and Phe183
Show others...
2012 (English)In: Annals of Clinical and Laboratory Science, ISSN 0091-7370, E-ISSN 1550-8080, Vol. 42, no 3, p. 231-242Article in journal (Refereed) Published
Abstract [en]

Bax-mediated permeabilization of the outer mitochondrial membrane and release of apoptogenic factors into the cytosol are key events that occur during apoptosis. Likewise, apoptosis is associated with permeabilization of the lysosomal membrane and release of lysosomal cathepsins into the cytosol. This report identifies proteolytically active cathepsin D as an important component of apoptotic signaling following lysosomal membrane permeabilization in fibroblasts. Lysosome-mediated cell death is associated with degradation of Bax sequestering 14-3-3 proteins, cleavage of the Box activator Bid, and translocation of Box to mitochondria, all of which were cathepsin D-dependent. Processing of Bid could be reproduced by enforced lysosomal membrane permeabilization, using the lysosomotropic detergent O-methyl-serine dodecylamine hydrochloride (MSDH). We identified three cathepsin D-specific cleavage sites in Bid, Phe24, Trp48, and Phe183. Cathepsin D-cleaved Bid induced Bax-mediated release of cytochrome c from purified mitochondria, indicating that the fragments generated are functionally active. Moreover, apoptosis was associated with cytosolic acidification, thereby providing a more favorable environment for the cathepsin D-mediated cleavage of Bid. Our study suggests that cytosolic cathepsin D triggers Bax-mediated cytochrome c release by proteolytic activation of Bid.

Place, publisher, year, edition, pages
Institute for Clinical Science, 2012
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-80794 (URN)000307091500001 ()
Note

Funding Agencies|Swedish Cancer Society||Swedish Research Council||Swedish Society for Medical Research||County Council of Ostergotland||foundation of Lars Hierta||foundation of Tore Nilson||foundation of Magn||foundation of Bergvall||foundation of Stohne||foundation of Hedberg||

The original title of this article in Manuscript was: Cathepsin D-specific processing of Bid at Phe24, Trp48, and Phe183

Available from: 2012-08-30 Created: 2012-08-30 Last updated: 2017-12-07Bibliographically approved
Farnebo, L., Jerhammar, F., Ceder, R., Grafström, R. C., Vainikka, L., Thunell, L., . . . Roberg, K. (2011). Combining factors on protein and gene level to predict radioresponse in head and neck cancer cell lines. Journal of Oral Pathology & Medicine, 40(10), 739-746
Open this publication in new window or tab >>Combining factors on protein and gene level to predict radioresponse in head and neck cancer cell lines
Show others...
2011 (English)In: Journal of Oral Pathology & Medicine, ISSN 0904-2512, E-ISSN 1600-0714, Vol. 40, no 10, p. 739-746Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Radiotherapy is the main therapy for head and neck squamous cell carcinoma (HNSCC); however, treatment resistance and local recurrence are significant problems, highlighting the need for predictive markers. In this study, we evaluated selected proteins, mutations, and single nucleotide polymorphisms (SNPs) involved in apoptosis, cell proliferation, and DNA repair alone or combined as predictive markers for radioresponse in 42 HNSCC cell lines.

METHODS: The expression of epidermal growth factor receptor, survivin, Bax, Bcl-2, Bcl-XL, cyclooxygenase-2, and heat shock protein 70 was analyzed by ELISA. Furthermore, mutations and SNPs in the p53 gene as well as SNPs in the MDM2, XRCC1, and XRCC3 genes were analyzed for their relation to radioresponse. To enable the evaluation of the predictive value of several factors combined, each cell line was allocated points based on the number of negative points (NNP) system, and the NNP sum was correlated with radioresponse.

RESULTS: Survivin was the only factor that alone was significantly correlated with the intrinsic radiosensitivity (r=0.36, p=0.02). The combination of survivin, Bax, Bcl-2, Bcl-XL, cyclooxygenase-2, and the p53 Arg72Pro polymorphism was found to most strongly correlate with radioresponse (r=0.553, p<0.001).

CONCLUSION: These data indicate that the intrinsic radiosensitivity of 42 HNSCC cell lines can be predicted by a panel of factors on both the protein and gene levels. Moreover, among the investigated factors, survivin was the most promising biomarker of radioresponse.

Place, publisher, year, edition, pages
John Wiley and sons, 2011
Keywords
head and neck tumors, radiotherapy, survivin, Bcl-2 family, p53 Arg72Pro
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-61585 (URN)10.1111/j.1600-0714.2011.01036.x (DOI)000296607200002 ()
Note
Funding agencies|Swedish Laryng Foundation||County Council of Ostergotland (OLL)||Swedish Cancer Foundation||Foundation of Olle Engkvist||Linkoping University Hospital||Available from: 2010-11-16 Created: 2010-11-16 Last updated: 2017-12-12Bibliographically approved
Johansson, A.-C., Appelqvist, H., Nilsson, C., Kågedal, K., Roberg, K. & Öllinger, K. (2010). Regulation of apoptosis-associated lysosomal membrane permeabilization. APOPTOSIS, 15(5), 527-540
Open this publication in new window or tab >>Regulation of apoptosis-associated lysosomal membrane permeabilization
Show others...
2010 (English)In: APOPTOSIS, ISSN 1360-8185, Vol. 15, no 5, p. 527-540Article in journal (Refereed) Published
Abstract [en]

Lysosomal membrane permeabilization (LMP) occurs in response to a large variety of cell death stimuli causing release of cathepsins from the lysosomal lumen into the cytosol where they participate in apoptosis signaling. In some settings, apoptosis induction is dependent on an early release of cathepsins, while under other circumstances LMP occurs late in the cell death process and contributes to amplification of the death signal. The mechanism underlying LMP is still incompletely understood; however, a growing body of evidence suggests that LMP may be governed by several distinct mechanisms that are likely engaged in a death stimulus- and cell-type-dependent fashion. In this review, factors contributing to permeabilization of the lysosomal membrane including reactive oxygen species, lysosomal membrane lipid composition, proteases, p53, and Bcl-2 family proteins, are described. Potential mechanisms to safeguard lysosomal integrity and confer resistance to lysosome-dependent cell death are also discussed.

Place, publisher, year, edition, pages
Springer Science Business Media, 2010
Keywords
Lysosome, Lysosomal release, Caspases, Calpains, Hsp, LAMP
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-55061 (URN)10.1007/s10495-009-0452-5 (DOI)000276489900001 ()
Note

The original publication is available at www.springerlink.com: Ann-Charlotte Johansson, Hanna Appelqvist, Cathrine Nilsson, Katarina Kågedal, Karin Roberg and Karin Öllinger, Regulation of apoptosis-associated lysosomal membrane permeabilization, 2010, APOPTOSIS, (15), 5, 527-540. http://dx.doi.org/10.1007/s10495-009-0452-5 Copyright: Springer Science Business Media http://www.springerlink.com/

Available from: 2010-04-28 Created: 2010-04-28 Last updated: 2017-08-30
Organisations

Search in DiVA

Show all publications