nach oben

International Journal of Clinical Oncology

Erschienen in:

27.02.2020 | Original Article

Calpain suppresses cell growth and invasion of glioblastoma multiforme by producing the cleavage of filamin A

verfasst von: Lin Cai, Qun Li, Wenfeng Li, Chengde Wang, Ming Tu, Zhangzhang Zhu, Zhipeng Su, Xianghe Lu

Erschienen in: International Journal of Clinical Oncology | Ausgabe 6/2020

Einloggen, um Zugang zu erhalten

Abstract

Background

Filamin A is the most widely expressed isoform of filamin in mammalian tissues. It can be hydrolyzed by Calpain, producing a 90-kDa carboxyl-terminal fragment (ABP90). Calpeptin is a chemical inhibitor of Calpain, which can inhibit this effect. It has been shown that ABP90 acts as a transcription factor which is involved in mediating cell signaling. However, the significance of ABP90 and its clinical signature with underlying mechanisms have not been well studied in glioblastoma multiforme (GBM).

Methods

ABP90 protein was measured in 36 glioma patients by Western blot. Human GBM cell lines U87 and A172 were used to clarify the precise role of ABP90. CCK-8 assay was used to analyze the cell viability. Transwell invasion assay and wound healing assay were used to analyze the migration and invasion. Expression of matrix metalloproteinase 2/tissue inhibitors of metalloproteinase 2 (MMP2/TIMP2) protein was analyzed by Western blot.

Results

ABP90 protein expression was lower in GBM tissues. The patients with low ABP90 protein expression had a shorter OS time (p = 0.046). After being treated with Calpain, the expression of ABP90 was upregulated, which led to a decline of cell viability, enhanced the efficacy of temozolomide and restrained the cell invasion. Calpeptin could inhibit the effect. The mechanism might be involved in the balance of MMP2/TIMP2.

Conclusions

Our present data suggest that ABP90 expression is a significant prognostic factor and may play an important role in cell viability, chemotherapeutic sensitivity and invasion of GBM.

Nur mit Berechtigung zugänglich

Stupp R, Mason WP, van den Bent MJ et al (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352(10):987–996PubMedCrossRef

Verhaak RG, Hoadley KA, Purdom E et al (2010) Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell 17(1):98–110PubMedPubMedCentralCrossRef

Stupp R, Hegi ME, Mason WP et al (2009) Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol 10(5):459–466PubMedCrossRef

Van Meir EG, Hadjipanayis CG, Norden AD et al (2010) Exciting new advances in neuro-oncology: the avenue to a cure for malignant glioma. CA Cancer J Clin 60(3):166–193PubMedPubMedCentralCrossRef

Purow B, Schiff D (2009) Advances in the genetics of glioblastoma: are we reaching critical mass? Nat Rev Neurol 5(8):419–426PubMedPubMedCentralCrossRef

Nakamura F, Stossel TP, Hartwig JH (2011) The filamins: organizers of cell structure and function. Cell Adhes Migr 5(2):160–169CrossRef

Berrou E, Adam F, Lebret M et al (2017) Gain-of-function mutation in filamin A potentiates platelet integrin alphaIIbbeta3 activation. Arterioscler Thromb Vasc Biol 37(6):1087–1097PubMedCrossRef

Gorlin JB, Yamin R, Egan S et al (1990) Human endothelial actin-binding protein (ABP-280, nonmuscle filamin): a molecular leaf spring. J Cell Biol 111(3):1089–1105PubMedCrossRef

van der Flier A, Sonnenberg A (2001) Structural and functional aspects of filamins. Biochem Biophys Acta 1538(2–3):99–117PubMedCrossRef

10.

Deng W, Lopez-Camacho C, Tang JY et al (2012) Cytoskeletal protein filamin A is a nucleolar protein that suppresses ribosomal RNA gene transcription. Proc Natl Acad Sci USA 109(5):1524–1529PubMedCrossRefPubMedCentral

11.

Mooso BA, Vinall RL, Tepper CG et al (2012) Enhancing the effectiveness of androgen deprivation in prostate cancer by inducing Filamin A nuclear localization. Endocr Relat Cancer 19(6):759–777PubMedCrossRef

12.

Planaguma J, Minsaas L, Pons M et al (2012) Filamin A-hinge region 1-EGFP: a novel tool for tracking the cellular functions of filamin A in real-time. PLoS ONE 7(8):e40864PubMedPubMedCentralCrossRef

13.

Liu T, Mendes DE, Berkman CE (2014) Prolonged androgen deprivation leads to overexpression of calpain 2: implications for prostate cancer progression. Int J Oncol 44(2):467–472PubMedCrossRef

14.

Hastings MH, Gong K, Freibauer A et al (2017) Novel calpain families and novel mechanisms for calpain regulation in Aplysia. PLoS ONE 12(10):e0186646PubMedPubMedCentralCrossRef

15.

Savoy RM, Ghosh PM (2013) The dual role of filamin A in cancer: can't live with (too much of) it, can't live without it. Endocr Relat Cancer 20(6):R341–356PubMedPubMedCentralCrossRef

16.

Chantaravisoot N, Wongkongkathep P, Loo JA et al (2015) Significance of filamin A in mTORC2 function in glioblastoma. Mol Cancer 14:127PubMedPubMedCentralCrossRef

17.

Robertson SP, Twigg SR, Sutherland-Smith AJ et al (2003) Localized mutations in the gene encoding the cytoskeletal protein filamin A cause diverse malformations in humans. Nat Genet 33(4):487–491PubMedCrossRef

18.

Saido TC, Sorimachi H, Suzuki K (1994) Calpain: new perspectives in molecular diversity and physiological-pathological involvement. FASEB J 8(11):814–822PubMedCrossRef

19.

Ray SK, Wilford GG, Crosby CV et al (1999) Diverse stimuli induce calpain overexpression and apoptosis in C6 glioma cells. Brain Res 829(1–2):18–27PubMedCrossRef

20.

Ray SK, Fidan M, Nowak MW et al (2000) Oxidative stress and Ca²⁺ influx upregulate calpain and induce apoptosis in PC12 cells. Brain Res 852(2):326–334PubMedCrossRef

21.

Yang Z, Lin F, Robertson CS et al (2014) Dual vulnerability of TDP-43 to calpain and caspase-3 proteolysis after neurotoxic conditions and traumatic brain injury. J Cereb Blood Flow Metab 34(9):1444–1452PubMedPubMedCentralCrossRef

22.

Catzavelos C, Bhattacharya N, Ung YC et al (1997) Decreased levels of the cell-cycle inhibitor p27Kip1 protein: prognostic implications in primary breast cancer. Nat Med 3(2):227–230PubMedCrossRef

23.

Chappuis PO, Donato E, Goffin JR et al (2005) Cyclin E expression in breast cancer: predicting germline BRCA1 mutations, prognosis and response to treatment. Ann Oncol 16(5):735–742PubMedCrossRef

24.

Shao QQ, Zhang TP, Zhao WJ et al (2016) Filamin A: insights into its exact role in cancers. Pathol Oncol Res POR 22(2):245–252PubMedCrossRef

25.

Fucini P, Koppel B, Schleicher M et al (1999) Molecular architecture of the rod domain of the Dictyostelium gelation factor (ABP120). J Mol Biol 291(5):1017–1023PubMedCrossRef

26.

Krebs K, Ruusmann A, Simonlatser G et al (2015) Expression of FLNa in human melanoma cells regulates the function of integrin alpha1beta1 and phosphorylation and localisation of PKB/AKT/ERK1/2 kinases. Eur J Cell Biol 94(12):564–575PubMedCrossRef

27.

Sun GG, Lu YF, Zhang J et al (2014) Filamin A regulates MMP-9 expression and suppresses prostate cancer cell migration and invasion. Tumour Biol 35(4):3819–3826PubMedCrossRef

28.

Xu Y, Bismar TA, Su J et al (2010) Filamin A regulates focal adhesion disassembly and suppresses breast cancer cell migration and invasion. J Exp Med 207(11):2421–2437PubMedPubMedCentralCrossRef

29.

Zhang K, Zhu T, Gao D et al (2014) Filamin A expression correlates with proliferation and invasive properties of human metastatic melanoma tumors: implications for survival in patients. J Cancer Res Clin Oncol 140(11):1913–1926PubMedCrossRefPubMedCentral

30.

Wieczorek K, Wiktorska M, Sacewicz-Hofman I et al (2017) Filamin A upregulation correlates with Snail-induced epithelial to mesenchymal transition (EMT) and cell adhesion but its inhibition increases the migration of colon adenocarcinoma HT29 cells. Exp Cell Res 359(1):163–170PubMedCrossRef

31.

Wensheng D (2012) Cytoskeletal protein filamin A is a nucleolar protein that suppresses ribosomal RNA gene transcription. Proc Natl Acad Sci USA 5(109):1524–1529

32.

Storr SJ, Carragher NO, Frame MC et al (2011) The calpain system and cancer. Nat Rev Cancer 11(5):364–374PubMedCrossRef

33.

Wu HY, Lynch DR (2006) Calpain and synaptic function. Mol Neurobiol 33(3):215–236PubMedCrossRef

34.

Chen J, Wu Y, Zhang L et al (2019) Evidence for calpains in cancer metastasis. J Cell Physiol 234(6):8233–8240PubMedCrossRef

35.

Liu J, Liu MC, Wang KK (2008) Calpain in the CNS: from synaptic function to neurotoxicity. Sci Signal 1(14):re1PubMedCrossRef

36.

Su Y, Cui Z, Li Z et al (2006) Calpain-2 regulation of VEGF-mediated angiogenesis. FASEB J 20(9):1443–1451PubMedCrossRef

37.

Bramhall SR, Neoptolemos JP, Stamp GW et al (1997) Imbalance of expression of matrix metalloproteinases (MMPs) and tissue inhibitors of the matrix metalloproteinases (TIMPs) in human pancreatic carcinoma. J Pathol 182(3):347–355PubMedCrossRef

38.

Fillmore HL, VanMeter TE, Broaddus WC (2001) Membrane-type matrix metalloproteinases (MT-MMPs): expression and function during glioma invasion. J Neurooncol 53(2):187–202PubMedCrossRef

39.

Pornchai OC, Rhys-Evans PH, Eccles SA (2001) Expression of matrix metalloproteinases and their inhibitors correlates with invasion and metastasis in squamous cell carcinoma of the head and neck. Arch Otolaryngol Head Neck Surg 127(7):813–820

40.

Theret N, Musso O, Turlin B et al (2001) Increased extracellular matrix remodeling is associated with tumor progression in human hepatocellular carcinomas. Hepatology 34(1):82–88PubMedCrossRef

41.

Kallakury BV, Karikehalli S, Haholu A et al (2001) Increased expression of matrix metalloproteinases 2 and 9 and tissue inhibitors of metalloproteinases 1 and 2 correlate with poor prognostic variables in renal cell carcinoma. Clin Cancer Res 7(10):3113–3119PubMed

42.

Tanaka K, Iwamoto Y, Ito Y et al (1995) Cyclic AMP-regulated synthesis of the tissue inhibitors of metalloproteinases suppresses the invasive potential of the human fibrosarcoma cell line HT1080. Cancer Res 55(13):2927–2935PubMed

Titel: Calpain suppresses cell growth and invasion of glioblastoma multiforme by producing the cleavage of filamin A
verfasst von: Lin Cai
Qun Li
Wenfeng Li
Chengde Wang
Ming Tu
Zhangzhang Zhu
Zhipeng Su
Xianghe Lu
Publikationsdatum: 27.02.2020
Verlag: Springer Singapore
Erschienen in: International Journal of Clinical Oncology / Ausgabe 6/2020
Print ISSN: 1341-9625
Elektronische ISSN: 1437-7772
DOI: https://doi.org/10.1007/s10147-020-01636-7

Springer Medizin

Calpain suppresses cell growth and invasion of glioblastoma multiforme by producing the cleavage of filamin A

Abstract

Background

Methods

Results

Conclusions

Neu im Fachgebiet Onkologie

Adjuvante Immuntherapie verlängert Leben bei RCC

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

Bei Senioren mit Prostatakarzinom auf Anämie achten!

ICI-Therapie in der Schwangerschaft wird gut toleriert

Update Onkologie

Springer Medizin

Abstract

Background

Methods

Results

Conclusions

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 6/2020

Down-regulation of miR-200c associates with poor prognosis of oral squamous cell carcinoma

Clinical impact of revisions to the WHO classification of diffuse gliomas and associated future problems

Salivary metabolites to detect patients with cancer: a systematic review

Evaluation of a routine second curettage for hydatidiform mole: a cohort study

Efficacy of neoadjuvant and adjuvant chemotherapy for localized and locally advanced upper tract urothelial carcinoma: a systematic review and meta-analysis

Efficacy and feasibility of S-1 plus oxaliplatin (C-SOX) for treating patients with stage III colon cancer (KSCC1303): final analysis of 3-year disease-free survival

Neu im Fachgebiet Onkologie

Adjuvante Immuntherapie verlängert Leben bei RCC

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

Bei Senioren mit Prostatakarzinom auf Anämie achten!

ICI-Therapie in der Schwangerschaft wird gut toleriert

Update Onkologie