Expression of karyopherin alfa 2 and karyopherin beta 1 correlate with poor prognosis in gastric cancer

Ohhara Y. · Kinoshita I. · Suzuki A. · Imagawa M. · Taguchi J. · Noguchi T. · Takeuchi S. · Shimizu Y. · Seki H. · Suzuki J. · Dosaka-Akita H.

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Article / Publication Details Abstract

Introduction: Karyopherin alfa 2 (KPNA2) and karyopherin beta 1 (KPNB1), constitute nuclear transport protein complexes involved in nuclear import, and are significant in tumor progression. Although high KPNA2 expression was associated with poor prognosis in solid tumors, the relationship between KPNA2 and KPNB1 expression and their prognostic role in gastric cancer (GC) remains unclear. Methods: Immunohistochemistry was used to correlate the expression of KPNA2 and KPNB1 with various features, including clinicopathologic characteristics in 130 patients with GC and survival in 94 patients with invasive lesions extending to the submucosa or deeper. Results: High expression of KPNA2 and KPNB1 was found in 25% and 36% of the patients, respectively. Both were significantly related to tumor depth, lymph node metastasis, lymphatic invasion, venous invasion, and Ki-67 expression. KPNA2 expression was significantly related to that of KPNB1 (P

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References Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424. Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): A phase 3, open-label, randomised controlled trial. Lancet. 2010;376(9742):687–97. Chook YM, Blobel G. Karyopherins and nuclear import. Curr Opin Struct Biol. 2001;11(6):703–15. Stewart M. Molecular mechanism of the nuclear protein import cycle. Nat Rev Mol Cell Biol. 2007;8(3):195–208. Fukuda M, Asano S, Nakamura T, Adachi M, Yoshida M, Yanagida M, et al. CRM1 is responsible for intracellular transport mediated by the nuclear export signal. Nature. 1997;390(6657):308–11. Ström AC, Weis K. Importin-beta-like nuclear transport receptors. Genome Biol. 2001;2(6):3008. ):Reviews van der Watt PJ, Ngarande E, Leaner VD. Overexpression of Kpnβ1 and Kpnα2 importin proteins in cancer derives from deregulated E2F activity. PLOS One. 2011;6(11):e27723. Dankof A, Fritzsche FR, Dahl E, Pahl S, Wild P, Dietel M, et al. KPNA2 protein expression in invasive breast carcinoma and matched peritumoral ductal carcinoma in situ. Virchows Arch. 2007;451(5):877–81. Gluz O, Wild P, Meiler R, Diallo-Danebrock R, Ting E, Mohrmann S, et al. Nuclear karyopherin α2 expression predicts poor survival in patients with advanced breast cancer irrespective of treatment intensity. Int J Cancer. 2008;123(6):1433–8. Dahl E, Kristiansen G, Gottlob K, Klaman I, Ebner E, Hinzmann B, et al. Molecular profiling of laser-microdissected matched tumor and normal breast tissue identifies karyopherin α2 as a potential novel prognostic marker in breast cancer. Clin Cancer Res. 2006;12(13):3950–60. Li XL, Jia LL, Shi MM, Li X, Li ZH, Li HF, et al. Downregulation of KPNA2 in non-small-cell lung cancer is associated with Oct4 expression. J Transl Med. 2013;11(1):232. Mortezavi A, Hermanns T, Seifert HH, Baumgartner MK, Provenzano M, Sulser T, et al. KPNA2 expression is an independent adverse predictor of biochemical recurrence after radical prostatectomy. Clin Cancer Res. 2011;17(5):1111–21. Zheng M, Tang L, Huang L, Ding H, Liao WT, Zeng MS, et al. Overexpression of karyopherin-2 in epithelial ovarian cancer and correlation with poor prognosis. Obstet Gynecol. 2010;116(4):884–91. Altan B, Yokobori T, Mochiki E, Ohno T, Ogata K, Ogawa A, et al. Nuclear karyopherin-α2 expression in primary lesions and metastatic lymph nodes was associated with poor prognosis and progression in gastric cancer. Carcinogenesis. 2013;34(10):2314–21. Li C, Ji L, Ding ZY, Zhang QD, Huang GR. Overexpression of KPNA2 correlates with poor prognosis in patients with gastric adenocarcinoma. Tumor Biol. 2013;34(2):1021–6. van der Watt PJ, Maske CP, Hendricks DT, Parker MI, Denny L, Govender D, et al. The Karyopherin proteins, Crm1 and Karyopherin β1, are overexpressed in cervical cancer and are critical for cancer cell survival and proliferation. Int J Cancer. 2009;124(8):1829–40. Japanese Gastric Cancer Association. Japanese classification of gastric carcinoma: 2nd English edition -. Gastric Cancer. 1998;1(1):10–24. Yang L, Hu B, Zhang Y, Qiang S, Cai J, Huang W, et al. Suppression of the nuclear transporter-KPNβ1 expression inhibits tumor proliferation in hepatocellular carcinoma. Med Oncol. 2015;32(4):128. Zhou LN, Tan Y, Li P, Zeng P, Chen MB, Tian Y, et al. Prognostic value of increased KPNA2 expression in some solid tumors: a systematic review and meta-analysis. Oncotarget. 2017;8(1):303–14. Zhu J, Wang Y, Huang H, Yang Q, Cai J, Wang Q, et al. Upregulation of KPNβ1 in gastric cancer cell promotes tumor cell proliferation and predicts poor prognosis. Tumor Biol. 2016;37(1):661–72. Tseng SF, Chang CY, Wu KJ, Teng SC. Importin KPNA2 is required for proper nuclear localization and multiple functions of NBS1. J Biol Chem. 2005;280(47):39594–600. Zannini L, Lecis D, Lisanti S, Benetti R, Buscemi G, Schneider C, et al. Karyopherin-α2 protein interacts with Chk2 and contributes to its nuclear import. J Biol Chem. 2003;278(43):42346–51. Teng SC, Wu KJ, Tseng SF, Wong CW, Kao L. Importin KPNA2, NBS1, DNA repair and tumorigenesis. J Mol Histol. 2006;37(5–7):293–9. Alshareeda AT, Negm OH, Green AR, Nolan CC, Tighe P, Albarakati N. KPNA2 is a nuclear export protein that contributes to aberrant localisation of key proteins and poor prognosis of breast cancer. Br J Cancer. 2015;112(12):1929–37. Stelma T, Chi A, van der Watt PJ, Verrico A, Lavia P, Leaner VD. Targeting nuclear transporters in cancer: diagnostic, prognostic and therapeutic potential. IUBMB Life. 2016;68(4):268–80. Carden S, van der Watt P, Chi A, Ajayi-Smith A, Hadley K, Leaner VD. A tight balance of karyopherin β1 expression is required in cervical cancer cells. BMC Cancer. 2018;18(1):1123. van der Watt PJ, Chi A, Stelma T, Stowell C, Strydom E, Carden S, et al. Targeting the nuclear import receptor Kpnβ1 as an anticancer therapeutic. Mol Cancer Ther. 2016;15(4):560–73. Wang T, Huang Z, Huang N, Peng Y, Gao M, Wang X, et al. Inhibition of KPNB1 inhibits proliferation and promotes apoptosis of chronic myeloid leukemia cells through regulation of E2F1. Onco Targets Ther. 2019;12:10455–67. Zhu ZC, Liu JW, Li K, Zheng J, Xiong ZQ. KPNB1 inhibition disrupts proteostasis and triggers unfolded protein response-mediated apoptosis in glioblastoma cells. Oncogene. 2018;37(22):2936–52. Zhang Y, Li KF. Karyopherin β1 deletion suppresses tumor growth and metastasis in colorectal cancer (CRC) by reducing MET expression. Biomed Pharmacother. 2019;120:109127. Chook YM, Süel KE. Nuclear import by karyopherin-βs: recognition and inhibition. Biochim Biophys Acta. 2011;1813(9):1593–606. Forwood JK, Lam MH, Jans DA. Nuclear import of Creb and AP-1 transcription factors requires importin-β1 and ran but is independent of importin-α. Biochemistry. 2001;40(17):5208–17. Chi RA, van der Watt P, Wei W, Birrer MJ, Leaner VD. Inhibition of Kpnβ1 mediated nuclear import enhances cisplatin chemosensitivity in cervical cancer. BMC Cancer. 2021;21(1):106. Abdul Razak AR, Mau-Soerensen M, Gabrail NY, Gerecitano JF, Shields AF, Unger TJ, et al. First-in-class, first-in-human phase I study of selinexor, a selective inhibitor of nuclear export, in patients with advanced solid tumors. J Clin Oncol. 2016;34(34):4142–50. Kalakonda N, Maerevoet M, Cavallo F, Follows G, Goy A, Vermaat JSP, et al. Selinexor in patients with relapsed or refractory diffuse large B-cell lymphoma (SADAL): a single-arm, multinational, multicentre, open-label, phase 2 trial. Lancet Haematol. 2020;7(7):e511–22. Chari A, Vogl DT, Gavriatopoulou M, Nooka AK, Yee AJ, Huff CA, et al. Oral selinexor-dexamethasone for triple-class refractory multiple myeloma. N Engl J Med. 2019;381(8):727–38. Article / Publication Details Copyright / Drug Dosage / Disclaimer Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
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