nach oben

Journal of Cancer Research and Clinical Oncology

Erschienen in:

23.02.2021 | Original Article – Cancer Research

Identification of oral squamous cell carcinoma markers MUC2 and SPRR1B downstream of TANGO

verfasst von: Tomonori Sasahira, Miyako Kurihara-Shimomura, Hiroyuki Shimomura, Anja Katrin Bosserhoff, Tadaaki Kirita

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 6/2021

Einloggen, um Zugang zu erhalten

Abstract

Purpose

Transport and Golgi organization protein 1 (TANGO) promotes angiogenesis and lymphangiogenesis in oral squamous cell carcinoma (OSCC). To elucidate the underlying mechanisms, this study aims to identify and characterize elements downstream of TANGO that mediate its involvement in OSCC.

Methods

In this study, microarray analysis compared gene expression between control and TANGO-repressed HSC3 cells. Protein expression in 213 OSCC tissue samples was analyzed immunohistochemically.

Results

TANGO repression decreased or increased expression of Mucin 20 (MUC20) and small proline-rich protein 1B (SPRR1B), respectively. MUC20 increased the growth and invasiveness of OSCC cells via altered matrix metalloproteinase (MMP)-2 and E-cadherin expression and c-met phosphorylation. MUC20 induced angiogenesis and lymphangiogenesis by activating vascular endothelial growth factors A and C. In well-differentiated OSCC, SPRR1B expression was high (P = 0.0091) and correlated with keratinization markers and promoted proliferation by inducing mitogen-activated protein kinase p38 phosphorylation. MUC20 expression correlated significantly with clinical stage (P = 0.0024), lymph node metastasis (P = 0.0036), and number of blood and lymph vessels (P < 0.0001). MUC20-expressing cases had a significantly worse prognosis than non-expressing cases (P < 0.0001).

Conclusion

MUC20 and SPRR1B located downstream of TANGO may be useful molecular markers for OSCC.

Arndt S, Bosserhoff AK (2006) TANGO is a tumor suppressor of malignant melanoma. Int J Cancer 119:2812–2820. https://doi.org/10.1002/ijc.22242CrossRefPubMed

Arndt S, Bosserhoff AK (2007) Reduced expression of TANGO in colon and hepatocellular carcinomas. Oncol Rep 18:885–891PubMed

Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68:394–424. https://doi.org/10.3322/caac.21492CrossRef

Chen CH et al (2013) MUC20 overexpression predicts poor prognosis and enhances EGF-induced malignant phenotypes via activation of the EGFR-STAT3 pathway in endometrial cancer. Gynecol Oncol 128:560–567. https://doi.org/10.1016/j.ygyno.2012.12.012CrossRefPubMed

Chen CH et al (2016) MUC20 promotes aggressive phenotypes of epithelial ovarian cancer cells via activation of the integrin β1 pathway. Gynecol Oncol 140:131–137. https://doi.org/10.1016/j.ygyno.2015.11.025CrossRefPubMed

Chen ST, Kuo TC, Liao YY, Lin MC, Tien YW, Huang MC (2018) Silencing of MUC20 suppresses the malignant character of pancreatic ductal adenocarcinoma cells through inhibition of the HGF/MET pathway. Oncogene 37:6041–6053. https://doi.org/10.1038/s41388-018-0403-0CrossRefPubMedPubMedCentral

Cho KH, Son YS, Lee DY, Chung EK, Hur KC, Hong SI, Fuchs E (1996) Calcipotriol (MC 903), a synthetic derivative of vitamin D3 stimulates differentiation of squamous carcinoma cell line in the raft culture. Anticancer Res 16:337–347PubMed

Fujimoto W, Nakanishi G, Arata J, Jetten AM (1997) Differential expression of human cornifin alpha and beta in squamous differentiating epithelial tissues and several skin lesions. J Invest Dermatol 108:200–204. https://doi.org/10.1111/1523-1747.ep12334240CrossRefPubMed

Gao H, Cong X, Zhou J, Guan M (2017) MicroRNA-222 influences migration and invasion through MIA3 in colorectal cancer. Cancer Cell Int 17:78. https://doi.org/10.1186/s12935-017-0447-1CrossRefPubMedPubMedCentral

Higuchi T et al (2004a) MUC20 suppresses the hepatocyte growth factor-induced Grb2-Ras pathway by binding to a multifunctional docking site of met. Mol Cell Biol 24:7456–7468. https://doi.org/10.1128/mcb.24.17.7456-7468.2004CrossRefPubMedPubMedCentral

Higuchi T et al (2004b) Molecular cloning, genomic structure, and expression analysis of MUC20, a novel mucin protein, up-regulated in injured kidney. J Biol Chem 279:1968–1979. https://doi.org/10.1074/jbc.M304558200CrossRefPubMed

Hippo Y et al (2001) Differential gene expression profiles of scirrhous gastric cancer cells with high metastatic potential to peritoneum or lymph nodes. Cancer Res 61:889–895PubMed

Kitamoto S, Yokoyama S, Higashi M, Yamada N, Takao S, Yonezawa S (2013) MUC1 enhances hypoxia-driven angiogenesis through the regulation of multiple proangiogenic factors. Oncogene 32:4614–4621. https://doi.org/10.1038/onc.2012.478CrossRefPubMed

Kitamura R et al (2012) Association of cytokeratin 17 expression with differentiation in oral squamous cell carcinoma. J Cancer Res Clin Oncol 138:1299–1310. https://doi.org/10.1007/s00432-012-1202-6CrossRefPubMedPubMedCentral

Kong X, Ding LJ, Wang ZX (2017) Mucin expression profile of benign and malignant cervical tissues and correlation with clinical-pathologic parameters. Eur J Gynaecol Oncol 38:350–355PubMed

Kurihara M et al (2013) Protumoral roles of melanoma inhibitory activity 2 in oral squamous cell carcinoma. Br J Cancer 108:1460–1469. https://doi.org/10.1038/bjc.2013.27CrossRefPubMedPubMedCentral

Kurihara-Shimomura M, Sasahira T, Shimomura H, Bosserhoff AK, Kirita T (2020) Mast cell chymase promotes angiogenesis and lymphangiogenesis mediated by activation of melanoma inhibitory activity gene family members in oral squamous cell carcinoma. Int J Oncol 56:1093–1100. https://doi.org/10.3892/ijo.2020.4996CrossRefPubMed

Li W et al (2001) The p38-MAPK/SAPK pathway is required for human keratinocyte migration on dermal collagen. J Invest Dermatol 117:1601–1611. https://doi.org/10.1046/j.0022-202x.2001.01608.xCrossRefPubMed

Ludovini V et al (2016) Gene identification for risk of relapse in stage I lung adenocarcinoma patients: a combined methodology of gene expression profiling and computational gene network analysis. Oncotarget 7:30561–30574. https://doi.org/10.18632/oncotarget.8723CrossRefPubMedPubMedCentral

Matsumura A et al (2013) HGF regulates VEGF expression via the c-Met receptor downstream pathways, PI3K/Akt, MAPK and STAT3, in CT26 murine cells. Int J Oncol 42:535–542. https://doi.org/10.3892/ijo.2012.1728CrossRefPubMed

Michifuri Y et al (2013) Small proline-rich protein-1B is overexpressed in human oral squamous cell cancer stem-like cells and is related to their growth through activation of MAP kinase signal. Biochem Biophys Res Commun 439:96–102. https://doi.org/10.1016/j.bbrc.2013.08.021CrossRefPubMed

Miranda-Filho A, Bray F (2020) Global patterns and trends in cancers of the lip, tongue and mouth. Oral Oncol 102:104551. https://doi.org/10.1016/j.oraloncology.2019.104551CrossRefPubMed

Momose F, Araida T, Negishi A, Ichijo H, Shioda S, Sasaki S (1989) Variant sublines with different metastatic potentials selected in nude mice from human oral squamous cell carcinomas. J Oral Pathol Med 18:391–395. https://doi.org/10.1111/j.1600-0714.1989.tb01570.xCrossRefPubMed

Morfoisse F et al (2014) Hypoxia induces VEGF-C expression in metastatic tumor cells via a HIF-1α-independent translation-mediated mechanism. Cell Rep 6:155–167. https://doi.org/10.1016/j.celrep.2013.12.011CrossRefPubMed

Naher L et al (2012) STAT3 signal transduction through interleukin-22 in oral squamous cell carcinoma. Int J Oncol 41:1577–1586. https://doi.org/10.3892/ijo.2012.1594CrossRefPubMedPubMedCentral

O'Sullivan B (2017) Head and neck tumours. In: Brierley JD, Gospodarowicz MK, Wittekind C (eds) UICC TNM classification of malignant tumours, 8 th edn. Wiley-Blackwell, Hoboken, pp 17–54

Patterson T, Vuong H, Liaw YS, Wu R, Kalvakolanu DV, Reddy SP (2001) Mechanism of repression of squamous differentiation marker, SPRR1B, in malignant bronchial epithelial cells: role of critical TRE-sites and its transacting factors. Oncogene 20:634–644. https://doi.org/10.1038/sj.onc.1204134CrossRefPubMed

Reddy SP, Adiseshaiah P, Shapiro P, Vuong H (2002) BMK1 (ERK5) regulates squamous differentiation marker SPRR1B transcription in Clara-like H441 cells. Am J Respir Cell Mol Biol 27:64–70. https://doi.org/10.1165/ajrcmb.27.1.20020003ocCrossRefPubMed

Reddy SP, Vuong H, Adiseshaiah P (2003) Interplay between proximal and distal promoter elements is required for squamous differentiation marker induction in the bronchial epithelium: role for ESE-1, Sp1, and AP-1 proteins. J Biol Chem 278:21378–21387. https://doi.org/10.1074/jbc.M212258200CrossRefPubMed

Riechers A, Bosserhoff AK (2014) Melanoma inhibitory activity in melanoma diagnostics and therapy - a small protein is looming large. Exp Dermatol 23:12–14. https://doi.org/10.1111/exd.12281CrossRefPubMed

Sasahira T, Kirita T (2018) Hallmarks of cancer-related newly prognostic factors of oral squamous cell carcinoma. Int J Mol Sci. https://doi.org/10.3390/ijms19082413CrossRefPubMedPubMedCentral

Sasahira T, Kirita T, Kuniyasu H (2014a) Update of molecular pathobiology in oral cancer: a review. Int J Clin Oncol 19:431–436. https://doi.org/10.1007/s10147-014-0684-4CrossRefPubMed

Sasahira T et al (2014b) Transport and Golgi organisation protein 1 is a novel tumour progressive factor in oral squamous cell carcinoma. Eur J Cancer 50:2142–2151. https://doi.org/10.1016/j.ejca.2014.05.006CrossRefPubMed

Sasahira T, Nishiguchi Y, Fujiwara R, Kurihara M, Kirita T, Bosserhoff AK, Kuniyasu H (2016) Storkhead box 2 and melanoma inhibitory activity promote oral squamous cell carcinoma progression. Oncotarget 7:26751–26764. https://doi.org/10.18632/oncotarget.8495CrossRefPubMedPubMedCentral

Sasahira T, Bosserhoff AK, Kirita T (2018) The importance of melanoma inhibitory activity gene family in the tumor progression of oral cancer. Pathol Int 68:278–286. https://doi.org/10.1111/pin.12672CrossRefPubMed

Schmidt J, Riechers A, Bosserhoff AK (2013) MIA–a new target protein for malignant melanoma therapy. Histol Histopathol 28:421–426. https://doi.org/10.14670/hh-28.421CrossRefPubMed

Schubert SA et al (2017) Evidence for genetic association between chromosome 1q loci and predisposition to colorectal neoplasia. Br J Cancer 117:1215–1223. https://doi.org/10.1038/bjc.2017.240CrossRefPubMedPubMedCentral

Shen LY, Wang H, Dong B, Yan WP, Lin Y, Shi Q, Chen KN (2016) Possible prediction of the response of esophageal squamous cell carcinoma to neoadjuvant chemotherapy based on gene expression profiling. Oncotarget 7:4531–4541. https://doi.org/10.18632/oncotarget.6554CrossRefPubMed

Shimomura H, Sasahira T, Nakashima C, Kurihara-Shimomura M, Kirita T (2019) Non-SMC condensin I complex subunit H (NCAPH) is associated with lymphangiogenesis and drug resistance in oral squamous cell carcinoma. J Clin Med. https://doi.org/10.3390/jcm9010072CrossRefPubMedPubMedCentral

Sloan P et al (2017) Malignant surface epithelial tumors. In: El-Naggar AK, Chan JKC, Rubin Grandis J, Takata T, Slootweg PJ (eds) WHO classification of head and neck tumours, 4th edn. World Health Organization, Lyon, pp 17–54

Swoboda A, Schanab O, Tauber S, Bilban M, Berger W, Petzelbauer P, Mikula M (2012) MET expression in melanoma correlates with a lymphangiogenic phenotype. Hum Mol Genet 21:3387–3396. https://doi.org/10.1093/hmg/dds171CrossRefPubMed

Wang H, Shen L, Lin Y, Shi Q, Yang Y, Chen K (2015) The expression and prognostic significance of Mucin 13 and Mucin 20 in esophageal squamous cell carcinoma. J Cancer Res Ther 11(Suppl 1):C74-79. https://doi.org/10.4103/0973-1482.163846CrossRefPubMed

Wilson DG et al (2011) Global defects in collagen secretion in a Mia3/TANGO1 knockout mouse. J Cell Biol 193:935–951. https://doi.org/10.1083/jcb.201007162CrossRefPubMedPubMedCentral

Woodward AM, Argüeso P (2014) Expression analysis of the transmembrane mucin MUC20 in human corneal and conjunctival epithelia. Invest Ophthalmol Vis Sci 55:6132–6138. https://doi.org/10.1167/iovs.14-15269CrossRefPubMedPubMedCentral

Xiao X et al (2013) Role of MUC20 overexpression as a predictor of recurrence and poor outcome in colorectal cancer. J Transl Med 11:151. https://doi.org/10.1186/1479-5876-11-151CrossRefPubMedPubMedCentral

Titel: Identification of oral squamous cell carcinoma markers MUC2 and SPRR1B downstream of TANGO
verfasst von: Tomonori Sasahira
Miyako Kurihara-Shimomura
Hiroyuki Shimomura
Anja Katrin Bosserhoff
Tadaaki Kirita
Publikationsdatum: 23.02.2021
Verlag: Springer Berlin Heidelberg
Erschienen in: Journal of Cancer Research and Clinical Oncology / Ausgabe 6/2021
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-021-03568-9

Neu im Fachgebiet Onkologie

Mehr Lebenszeit mit Abemaciclib bei fortgeschrittenem Brustkrebs?

24.05.2024 Mammakarzinom Nachrichten

In der MONARCHE-3-Studie lebten Frauen mit fortgeschrittenem Hormonrezeptor-positivem, HER2-negativem Brustkrebs länger, wenn sie zusätzlich zu einem nicht steroidalen Aromatasehemmer mit Abemaciclib behandelt wurden; allerdings verfehlte der numerische Zugewinn die statistische Signifikanz.

ADT zur Radiatio nach Prostatektomie: Wenn, dann wohl länger

24.05.2024 Prostatakarzinom Nachrichten

Welchen Nutzen es trägt, wenn die Strahlentherapie nach radikaler Prostatektomie um eine Androgendeprivation ergänzt wird, hat die RADICALS-HD-Studie untersucht. Nun liegen die Ergebnisse vor. Sie sprechen für länger dauernden Hormonentzug.

Das sind die führenden Symptome junger Darmkrebspatienten

23.05.2024 Leitsymptome in der Hausarztpraxis Nachrichten

Darmkrebserkrankungen in jüngeren Jahren sind ein zunehmendes Problem, das häufig längere Zeit übersehen wird, gerade weil die Patienten noch nicht alt sind. Welche Anzeichen Ärzte stutzig machen sollten, hat eine Metaanalyse herausgearbeitet.

„Überwältigende“ Evidenz für Tripeltherapie beim metastasierten Prostata-Ca.

22.05.2024 Prostatakarzinom Nachrichten

Patienten mit metastasiertem hormonsensitivem Prostatakarzinom sollten nicht mehr mit einer alleinigen Androgendeprivationstherapie (ADT) behandelt werden, mahnt ein US-Team nach Sichtung der aktuellen Datenlage. Mit einer Tripeltherapie haben die Betroffenen offenbar die besten Überlebenschancen.

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Die Highlights vom Kongress des American College of Cardiology 2024

Springer Medizin

Identification of oral squamous cell carcinoma markers MUC2 and SPRR1B downstream of TANGO