Skip to main content

Advertisement

SpringerLink
Log in

Silencing AHNAK promotes nasopharyngeal carcinoma progression by upregulating the ANXA2 protein

  • Research
  • Published:
Cellular Oncology Aims and scope Submit manuscript

Abstract

Purpose

Nasopharyngeal carcinoma (NPC) is an aggressive head and neck disease with a high incidence of distant metastases. Enlargeosomes are cytoplasmic organelles marked by, desmoyokin/AHNAK. This study aimed to evaluate the expression of AHNAK in NPC and its effect on enlargeosomes and to investigate the correlation between AHNAK expression levels and clinical NPC patient characteristics.

Methods

Primary nasopharyngeal carcinoma (NPC) and NPC specimens were evaluated by analyzing public data, and immunohistochemistry. Systematic in vitro and in vivo experiments were performed using different NPC-derived cell lines and mouse models.

Results

In this study, we detected AHNAK and Annexin A2(ANXA2), a protein coating the surface of enlargeosomes, in NPC samples. We found that AHNAK was down-regulated. Down-regulation of AHNAK was associated with poor overall survival in NPC patients. Moreover, transcription factor FOSL1-mediated transcriptional repression was responsible for the low expression of AHNAK by recruiting EZH2. Whereas Annexin A2 was upregulated in human NPC tissues. Upregulation of Annexin A2 was associated with lymph node metastasis and distant metastasis in NPC patients. Functional studies confirmed that silencing of AHNAK enhanced the growth, invasion, and metastatic properties of NPC cells both in vitro and in vivo. In terms of mechanism, loss of AHNAK led to an increase of annexin A2 protein level in NPC cells. Silencing ANXA2 restored NPC cells' migrative and invasive ability upon loss of AHNAK.

Conclusion

Here, we report AHNAK as a tumor suppressor in NPC, which may act through annexin A2 oncogenic signaling in enlargeosome, with potential implications for novel approaches to NPC treatment.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

Data Availability

All data that support the findings of this study are available from the corresponding authors upon reasonable request.

References

  1. L. Gong, D.L. Kwong, W. Dai, P. Wu, Y. Wang, A.W. Lee, X.Y. Guan, The stromal and immune landscape of nasopharyngeal carcinoma and its implications for precision medicine targeting the tumor microenvironment. Front. Oncol. 11, 744889 (2021)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Y.P. Chen, J.H. Yin, W.F. Li, H.J. Li, D.P. Chen, C.J. Zhang, J.W. Lv, Y.Q. Wang, X.M. Li, J.Y. Li, P.P. Zhang, Y.Q. Li, Q.M. He, X.J. Yang, Y. Lei, L.L. Tang, G.Q. Zhou, Y.P. Mao, C. Wei, K.X. Xiong, H.B. Zhang, S.D. Zhu, Y. Hou, Y. Sun, M. Dean, I. Amit, K. Wu, D.M. Kuang, G.B. Li, N. Liu, J. Ma, Single-cell transcriptomics reveals regulators underlying immune cell diversity and immune subtypes associated with prognosis in nasopharyngeal carcinoma. Cell Res. 30, 1024–1042 (2020)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. M. Yi, J. Cai, J. Li, S. Chen, Z. Zeng, Q. Peng, Y. Ban, Y. Zhou, X. Li, W. Xiong, G. Li, B. Xiang, Rediscovery of NF-kappaB signaling in nasopharyngeal carcinoma: How genetic defects of NF-kappaB pathway interplay with EBV in driving oncogenesis? J. Cell. Physiol. 233, 5537–5549 (2018)

    Article  CAS  PubMed  Google Scholar 

  4. W. Wang, M. Yi, R. Zhang, J. Li, S. Chen, J. Cai, Z. Zeng, X. Li, W. Xiong, L. Wang, G. Li, B. Xiang, Vimentin is a crucial target for anti-metastasis therapy of nasopharyngeal carcinoma. Mol. Cell. Biochem. 438, 47–57 (2018)

    Article  CAS  Google Scholar 

  5. X. Shi, J. Pan, F. Qiu, L. Wu, X. Zhang, Y. Feng, X. Gu, J. Zhao, W. Zheng, Multiscale transcriptomic integration reveals B-Cell depletion and T-Cell mistrafficking in nasopharyngeal carcinoma progression. Front. Cell Dev. Biol. 10, 857137 (2022)

    Article  PubMed  PubMed Central  Google Scholar 

  6. Y. Mo, Y. Wang, Y. Wang, X. Deng, Q. Yan, C. Fan, S. Zhang, S. Zhang, Z. Gong, L. Shi, Q. Liao, C. Guo, Y. Li, G. Li, Z. Zeng, W. Jiang, W. Xiong, B. Xiang, Circular RNA circPVT1 promotes nasopharyngeal carcinoma metastasis via the beta-TrCP/c-Myc/SRSF1 positive feedback loop. Mol. Cancer 21, 192 (2022)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. R. Miao, C.C. Dai, L. Mei, J. Xu, S.W. Sun, Y.L. Xing, L.S. Wu, M.H. Wang, J.F. Wei, KIAA1429 regulates cell proliferation by targeting c-Jun messenger RNA directly in gastric cancer. J. Cell. Physiol. 235, 7420–7432 (2020)

    Article  CAS  PubMed  Google Scholar 

  8. B.J. Gentil, C. Delphin, C. Benaud, J. Baudier, Expression of the giant protein AHNAK (desmoyokin) in muscle and lining epithelial cells. J. Histochem. Cytochem. 51, 339–348 (2003)

    Article  CAS  PubMed  Google Scholar 

  9. K. Tezuka, M. Suzuki, R. Sato, S. Kawarada, T. Terasaki, Y. Uchida, Activation of Annexin A2 signaling at the blood-brain barrier in a mouse model of multiple sclerosis. J. Neurochem. 160, 662–674 (2022)

    Article  CAS  PubMed  Google Scholar 

  10. T. Mirzapoiazova, F.E. Lennon, B. Mambetsariev, M. Allen, J. Riehm, V.A. Poroyko, P.A. Singleton, Extracellular vesicles from caveolin-enriched microdomains regulate hyaluronan-mediated sustained vascular integrity. Int. J. Cell Biol. 2015, 481493 (2015)

    Article  PubMed  PubMed Central  Google Scholar 

  11. A. Rezvanpour, L. Santamaria-Kisiel, G.S. Shaw, The S100A10-annexin A2 complex provides a novel asymmetric platform for membrane repair. J. Biol. Chem. 286, 40174–40183 (2011)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. A. Lorusso, C. Covino, G. Priori, A. Bachi, J. Meldolesi, E. Chieregatti, Annexin2 coating the surface of enlargeosomes is needed for their regulated exocytosis. EMBO J. 25, 5443–5456 (2006)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. A. Diaz-Diaz, D. Roca-Lema, A. Casas-Pais, G. Romay, G. Colombo, A. Concha, B. Grana, A. Figueroa, Heat shock protein 90 chaperone regulates the E3 Ubiquitin-Ligase Hakai protein stability. Cancers (Basel) 12, 215 (2020)

    Article  CAS  PubMed  Google Scholar 

  14. S. Jin, Y. Mi, J. Song, P. Zhang, Y. Liu, PRMT1-RBM15 axis regulates megakaryocytic differentiation of human umbilical cord blood CD34(+) cells. Exp. Ther. Med. 15, 2563–2568 (2018)

    CAS  PubMed  PubMed Central  Google Scholar 

  15. A. Pascal, E. Gallaud, R. Giet, C. Benaud, Annexin A2 and Ahnak control cortical NuMA-dynein localization and mitotic spindle orientation. J. Cell Sci. 135, 259344 (2022)

  16. I. Prada, E. Cocucci, G. Racchetti, J. Meldolesi, The Ca2+-dependent exocytosis of enlargeosomes is greatly reinforced by genistein via a non-tyrosine kinase-dependent mechanism. FEBS Lett. 581, 4932–4936 (2007)

    Article  CAS  PubMed  Google Scholar 

  17. E. Cocucci, G. Racchetti, P. Podini, M. Rupnik, J. Meldolesi, Enlargeosome, an exocytic vesicle resistant to nonionic detergents, undergoes endocytosis via a nonacidic route. Mol. Biol. Cell 15, 5356–5368 (2004)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. F. Colombo, G. Racchetti, J. Meldolesi, Neurite outgrowth induced by NGF or L1CAM via activation of the TrkA receptor is sustained also by the exocytosis of enlargeosomes. Proc. Natl. Acad. Sci. U. S. A. 111, 16943–16948 (2014)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. C. Schulte, G. Racchetti, R. D’Alessandro, J. Meldolesi, A new form of neurite outgrowth sustained by the exocytosis of enlargeosomes expressed under the control of REST. Traffic 11, 1304–1314 (2010)

    Article  CAS  PubMed  Google Scholar 

  20. G. Racchetti, A. Lorusso, C. Schulte, D. Gavello, V. Carabelli, R. D’Alessandro, J. Meldolesi, Rapid neurite outgrowth in neurosecretory cells and neurons is sustained by the exocytosis of a cytoplasmic organelle, the enlargeosome. J. Cell Sci. 123, 165–170 (2010)

    Article  CAS  PubMed  Google Scholar 

  21. W.C. Cho, J.E. Jang, K.H. Kim, B.C. Yoo, J.L. Ku, SORBS1 serves a metastatic role via suppression of AHNAK in colorectal cancer cell lines. Int. J. Oncol. 56, 1140–1151 (2020)

    CAS  PubMed  PubMed Central  Google Scholar 

  22. B. Chen, J. Wang, D. Dai, Q. Zhou, X. Guo, Z. Tian, X. Huang, L. Yang, H. Tang, X. Xie, AHNAK suppresses tumour proliferation and invasion by targeting multiple pathways in triple-negative breast cancer. J. Exp. Clin. Cancer Res. 36, 65 (2017)

    Article  PubMed  PubMed Central  Google Scholar 

  23. E. Shen, X. Wang, X. Liu, M. Lv, L. Zhang, G. Zhu, Z. Sun, MicroRNA-93-5p promotes epithelial-mesenchymal transition in gastric cancer by repressing tumor suppressor AHNAK expression. Cancer Cell Int. 20, 76 (2020)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Z.M. Liu, X.L. Yang, F. Jiang, Y.C. Pan, L. Zhang, Matrine involves in the progression of gastric cancer through inhibiting miR-93-5p and upregulating the expression of target gene AHNAK. J. Cell. Biochem. 121, 2467–2477 (2020)

    Article  CAS  PubMed  Google Scholar 

  25. J.W. Park, I.Y. Kim, J.W. Choi, H.J. Lim, J.H. Shin, Y.N. Kim, S.H. Lee, Y. Son, M. Sohn, J.K. Woo, J.H. Jeong, C. Lee, Y.S. Bae, J.K. Seong, AHNAK loss in mice promotes type II pneumocyte hyperplasia and lung tumor development. Mol. Cancer Res. 16, 1287–1298 (2018)

    Article  CAS  PubMed  Google Scholar 

  26. Z. Zhang, X. Liu, R. Huang, X. Liu, Z. Liang, T. Liu, Upregulation of nucleoprotein AHNAK is associated with poor outcome of pancreatic ductal adenocarcinoma prognosis via mediating epithelial-mesenchymal transition. J. Cancer 10, 3860–3870 (2019)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. J.S. Shafran, G.P. Andrieu, B. Gyorffy, G.V. Denis, BRD4 regulates metastatic potential of castration-resistant prostate cancer through AHNAK. Mol. Cancer Res. 17, 1627–1638 (2019)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. T.A. Silva, B. Smuczek, I.C. Valadao, L.M. Dzik, R.P. Iglesia, M.C. Cruz, A. Zelanis, A.S. de Siqueira, S.M. Serrano, G.S. Goldberg, R.G. Jaeger, V.M. Freitas, AHNAK enables mammary carcinoma cells to produce extracellular vesicles that increase neighboring fibroblast cell motility. Oncotarget 7, 49998–50016 (2016)

    Article  PubMed  PubMed Central  Google Scholar 

  29. W. Liu, Y. Pan, H. Zhu, Y. Zhou, H. Zhang, L. Liu, Q. Liu, G. Ji, CircRNA_0008194 functions as a ceRNA to promote invasion of hepatocellular carcinoma via inhibiting miR-190a/AHNAK signaling pathway. J. Clin. Lab. Anal. 36, e24286 (2022)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. R. Peng, P.F. Zhang, X. Yang, C.Y. Wei, X.Y. Huang, J.B. Cai, J.C. Lu, C. Gao, H.X. Sun, Q. Gao, D.S. Bai, G.M. Shi, A.W. Ke, J. Fan, Overexpression of RNF38 facilitates TGF-beta signaling by Ubiquitinating and degrading AHNAK in hepatocellular carcinoma. J. Exp. Clin. Cancer Res. 38, 113 (2019)

    Article  PubMed  PubMed Central  Google Scholar 

  31. V.V. Sobolev, A.Z. Khashukoeva, O.E. Evina, N.A. Geppe, S.N. Chebysheva, I.M. Korsunskaya, E. Tchepourina, A. Mezentsev, Role of the transcription factor FOSL1 in organ development and tumorigenesis. Int. J. Mol. Sci. 23, 1521 (2022)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. A. Usui, I. Hoshino, Y. Akutsu, H. Sakata, T. Nishimori, K. Murakami, M. Kano, K. Shuto, H. Matsubara, The molecular role of Fra-1 and its prognostic significance in human esophageal squamous cell carcinoma. Cancer 118, 3387–3396 (2012)

    Article  CAS  PubMed  Google Scholar 

  33. A.E. Sayan, R. Stanford, R. Vickery, E. Grigorenko, J. Diesch, K. Kulbicki, R. Edwards, R. Pal, P. Greaves, I. Jariel-Encontre, M. Piechaczyk, M. Kriajevska, J.K. Mellon, A.S. Dhillon, E. Tulchinsky, Fra-1 controls motility of bladder cancer cells via transcriptional upregulation of the receptor tyrosine kinase AXL. Oncogene 31, 1493–1503 (2012)

    Article  CAS  PubMed  Google Scholar 

  34. W. Debinski, D.M. Gibo, Fos-related antigen 1 modulates malignant features of glioma cells. Mol. Cancer Res. 3, 237–249 (2005)

    Article  CAS  PubMed  Google Scholar 

  35. J. Zhu, Y.P. Zhao, Y.Q. Zhang, Low expression of FOSL1 is associated with favorable prognosis and sensitivity to radiation/pharmaceutical therapy in lower grade glioma. Neurol. Res. 42, 522–527 (2020)

    Article  CAS  PubMed  Google Scholar 

  36. N. Feldker, F. Ferrazzi, H. Schuhwerk, S.A. Widholz, K. Guenther, I. Frisch, K. Jakob, J. Kleemann, D. Riegel, U. Bonisch, S. Lukassen, R.L. Eccles, C. Schmidl, M.P. Stemmler, T. Brabletz, S. Brabletz, Genome-wide cooperation of EMT transcription factor ZEB1 with YAP and AP-1 in breast cancer. EMBO J. 39, e103209 (2020)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. S. Yang, Y. Li, J. Gao, T. Zhang, S. Li, A. Luo, H. Chen, F. Ding, X. Wang, Z. Liu, MicroRNA-34 suppresses breast cancer invasion and metastasis by directly targeting Fra-1. Oncogene 32, 4294–4303 (2013)

    Article  CAS  PubMed  Google Scholar 

  38. J.E. Kim, B.G. Kim, Y. Jang, S. Kang, J.H. Lee, N.H. Cho, The stromal loss of miR-4516 promotes the FOSL1-dependent proliferation and malignancy of triple negative breast cancer. Cancer Lett. 469, 256–265 (2020)

    Article  CAS  PubMed  Google Scholar 

  39. S. Chen, T. Youhong, Y. Tan, Y. He, Y. Ban, J. Cai, X. Li, W. Xiong, Z. Zeng, G. Li, M. Yi, W. Liu, B. Xiang, EGFR-PKM2 signaling promotes the metastatic potential of nasopharyngeal carcinoma through induction of FOSL1 and ANTXR2. Carcinogenesis 41, 723–733 (2020)

    Article  CAS  PubMed  Google Scholar 

  40. S.W. He, C. Xu, Y.Q. Li, Y.Q. Li, Y. Zhao, P.P. Zhang, Y. Lei, Y.L. Liang, J.Y. Li, Q. Li, Y. Chen, S.Y. Huang, J. Ma, N. Liu, AR-induced long non-coding RNA LINC01503 facilitates proliferation and metastasis via the SFPQ-FOSL1 axis in nasopharyngeal carcinoma. Oncogene 39, 5616–5632 (2020)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. W. He, X. Zhou, Y. Mao, Y. Wu, X. Tang, S. Yan, S. Tang, CircCRIM1 promotes nasopharyngeal carcinoma progression via the miR-34c-5p/FOSL1 axis. Eur. J. Med. Res. 27, 59 (2022)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. T. Kitazawa, D. Machlab, O. Joshi, N. Maiorano, H. Kohler, S. Ducret, S. Kessler, H. Gezelius, C. Soneson, P. Papasaikas, G. Lopez-Bendito, M.B. Stadler, F.M. Rijli, A unique bipartite Polycomb signature regulates stimulus-response transcription during development. Nat. Genet. 53, 379–391 (2021)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. S. Ding, X. Wang, D. Lv, Y. Tao, S. Liu, C. Chen, Z. Huang, S. Zheng, Y. Wei, T. Kang, Y. Xia, EBF3 reactivation by inhibiting the EGR1/EZH2/HDAC9 complex promotes metastasis via transcriptionally enhancing vimentin in nasopharyngeal carcinoma. Cancer Lett. 527, 49–65 (2022)

    Article  CAS  PubMed  Google Scholar 

  44. L. Tan, Y. Qin, R. Xie, T. Xia, X. Duan, L. Peng, R. You, Y. Liu, X. Zou, M. Zhang, M. Lin, M. Chen, N6-methyladenosine-associated prognostic pseudogenes contribute to predicting immunotherapy benefits and therapeutic agents in head and neck squamous cell carcinoma. Theranostics 12, 7267–7288 (2022)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Y. Li, Q. He, X. Wen, X. Hong, X. Yang, X. Tang, P. Zhang, Y. Lei, Y. Sun, J. Zhang, Y. Wang, J. Ma, N. Liu, EZH2-DNMT1-mediated epigenetic silencing of miR-142-3p promotes metastasis through targeting ZEB2 in nasopharyngeal carcinoma. Cell Death Differ. 26, 1089–1106 (2019)

    Article  CAS  PubMed  Google Scholar 

  46. Y. Tan, Q. Chen, X. Li, Z. Zeng, W. Xiong, G. Li, X. Li, J. Yang, B. Xiang, M. Yi, Pyroptosis: a new paradigm of cell death for fighting against cancer. J. Exp. Clin. Cancer Res. 40, 153 (2021)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Y. Ban, Y. Tan, X. Li, X. Li, Z. Zeng, W. Xiong, G. Li, B. Xiang, M. Yi, RNA-binding protein YBX1 promotes cell proliferation and invasiveness of nasopharyngeal carcinoma cells via binding to AURKA mRNA. J. Cancer 12, 3315–3324 (2021)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. R. Yang, M. Yi, B. Xiang, Novel insights on lipid metabolism alterations in drug resistance in cancer. Front. Cell Dev. Biol. 10, 875318 (2022)

    Article  PubMed  PubMed Central  Google Scholar 

  49. J. Cai, M. Yi, Y. Tan, X. Li, G. Li, Z. Zeng, W. Xiong, B. Xiang, Natural product triptolide induces GSDME-mediated pyroptosis in head and neck cancer through suppressing mitochondrial hexokinase-IotaIota. J. Exp. Clin. Cancer Res. 40, 190 (2021)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. M. Yi, Y. Tan, L. Wang, J. Cai, X. Li, Z. Zeng, W. Xiong, G. Li, X. Li, P. Tan, B. Xiang, TP63 links chromatin remodeling and enhancer reprogramming to epidermal differentiation and squamous cell carcinoma development. Cell. Mol. Life Sci. 77, 4325–4346 (2020)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Y. Ban, P. Tan, J. Cai, J. Li, M. Hu, Y. Zhou, Y. Mei, Y. Tan, X. Li, Z. Zeng, W. Xiong, G. Li, X. Li, M. Yi, B. Xiang, LNCAROD is stabilized by m6A methylation and promotes cancer progression via forming a ternary complex with HSPA1A and YBX1 in head and neck squamous cell carcinoma. Mol. Oncol. 14, 1282–1296 (2020)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. J. Li, Y. Zhang, L. Wang, M. Li, J. Yang, P. Chen, J. Zhu, X. Li, Z. Zeng, G. Li, W. Xiong, J.B. McCarthy, B. Xiang, M. Yi, FOXA1 prevents nutrients deprivation induced autophagic cell death through inducing loss of imprinting of IGF2 in lung adenocarcinoma. Cell Death Dis. 13, 711 (2022)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. J. Li, W. Wang, S. Chen, J. Cai, Y. Ban, Q. Peng, Y. Zhou, Z. Zeng, X. Li, W. Xiong, G. Li, M. Yi, B. Xiang, FOXA1 reprograms the TGF-beta-stimulated transcriptional program from a metastasis promoter to a tumor suppressor in nasopharyngeal carcinoma. Cancer Lett. 442, 1–14 (2019)

    Article  CAS  PubMed  Google Scholar 

  54. J. Cai, S. Chen, M. Yi, Y. Tan, Q. Peng, Y. Ban, J. Yang, X. Li, Z. Zeng, W. Xiong, J.B. McCarthy, G. Li, X. Li, B. Xiang, DeltaNp63alpha is a super enhancer-enriched master factor controlling the basal-to-luminal differentiation transcriptional program and gene regulatory networks in nasopharyngeal carcinoma. Carcinogenesis 41, 1282–1293 (2020)

    Article  CAS  PubMed  Google Scholar 

  55. M.N. Ndlovu, C. Van Lint, K. Van Wesemael, P. Callebert, D. Chalbos, G. Haegeman, W. VandenBerghe, Hyperactivated NF-kappaB and AP-1 transcription factors promote highly accessible chromatin and constitutive transcription across the interleukin-6 gene promoter in metastatic breast cancer cells. Mol. Cell. Biol. 29, 5488–5504 (2009)

    Article  CAS  PubMed  Google Scholar 

  56. A. Ferraro, D. Mourtzoukou, V. Kosmidou, S. Avlonitis, G. Kontogeorgos, G. Zografos, A. Pintzas, EZH2 is regulated by ERK/AKT and targets integrin alpha2 gene to control Epithelial-Mesenchymal Transition and anoikis in colon cancer cells. Int. J. Biochem. Cell Biol. 45, 243–254 (2013)

    Article  CAS  PubMed  Google Scholar 

  57. V. Dallacasagrande, K.A. Hajjar, Annexin A2 in inflammation and host defense. Cells 9(6), 1499 (2020)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. B.M. Frey, B.F. Reber, B.S. Vishwanath, G. Escher, F.J. Frey, Annexin I modulates cell functions by controlling intracellular calcium release. FASEB J. 13, 2235–2245 (1999)

    Article  CAS  PubMed  Google Scholar 

  59. L. Vecchi, T.G. Araujo, F. Azevedo, S.T.S. Mota, V.M.R. Avila, M.A. Ribeiro, L.R. Goulart, Phospholipase A2 drives tumorigenesis and cancer aggressiveness through its interaction with Annexin A1. Cells 10(6), 1472 (2021)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Y. Huang, M. Jia, X. Yang, H. Han, G. Hou, L. Bi, Y. Yang, R. Zhang, X. Zhao, C. Peng, X. Ouyang, Annexin A2: The diversity of pathological effects in tumorigenesis and immune response. Int. J. Cancer 151, 497–509 (2022)

    Article  CAS  PubMed  Google Scholar 

  61. Y. Sun, G. Gao, J. Cai, Y. Wang, X. Qu, L. He, F. Liu, Y. Zhang, K. Lin, S. Ma, X. Yang, X. Qian, X. Zhao, Annexin A2 is a discriminative serological candidate in early hepatocellular carcinoma. Carcinogenesis 34, 595–604 (2013)

    Article  CAS  PubMed  Google Scholar 

  62. H. Zhai, S. Acharya, I. Gravanis, S. Mehmood, R.J. Seidman, K.R. Shroyer, K.A. Hajjar, S.E. Tsirka, Annexin A2 promotes glioma cell invasion and tumor progression. J. Neurosci. 31, 14346–14360 (2011)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. V.M. Kim, A.B. Blair, P. Lauer, K. Foley, X. Che, K. Soares, T. Xia, S.T. Muth, J. Kleponis, T.D. Armstrong, C.L. Wolfgang, E.M. Jaffee, D. Brockstedt, L. Zheng, Anti-pancreatic tumor efficacy of a Listeria-based, Annexin A2-targeting immunotherapy in combination with anti-PD-1 antibodies. J. Immunother. Cancer 7, 132 (2019)

    Article  PubMed  PubMed Central  Google Scholar 

  64. F. Pi, H. Zhang, H. Li, V. Thiviyanathan, D.G. Gorenstein, A.K. Sood, P. Guo, RNA nanoparticles harboring annexin A2 aptamer can target ovarian cancer for tumor-specific doxorubicin delivery. Nanomedicine 13, 1183–1193 (2017)

    Article  CAS  PubMed  Google Scholar 

  65. L.W. Qiu, Y.F. Liu, X.Q. Cao, Y. Wang, X.H. Cui, X. Ye, S.W. Huang, H.J. Xie, H.J. Zhang, Annexin A2 promotion of hepatocellular carcinoma tumorigenesis via the immune microenvironment. World J. Gastroenterol. 26, 2126–2137 (2020)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. C.Y. Chen, Y.S. Lin, C.L. Chen, P.Z. Chao, J.F. Chiou, C.C. Kuo, F.P. Lee, Y.F. Lin, Y.H. Sung, Y.T. Lin, C.F. Li, Y.J. Chen, C.H. Chen, Targeting annexin A2 reduces tumorigenesis and therapeutic resistance of nasopharyngeal carcinoma. Oncotarget 6, 26946–26959 (2015)

    Article  PubMed  PubMed Central  Google Scholar 

  67. B.J. Gentil, C. Benaud, C. Delphin, C. Remy, V. Berezowski, R. Cecchelli, O. Feraud, D. Vittet, J. Baudier, Specific AHNAK expression in brain endothelial cells with barrier properties. J. Cell. Physiol. 203, 362–371 (2005)

    Article  CAS  PubMed  Google Scholar 

  68. R. Han, K.P. Campbell, Dysferlin and muscle membrane repair. Curr. Opin. Cell Biol. 19, 409–416 (2007)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. E. Cocucci, G. Racchetti, P. Podini, J. Meldolesi, Enlargeosome traffic: exocytosis triggered by various signals is followed by endocytosis, membrane shedding or both. Traffic 8, 742–757 (2007)

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This study was supported in part by grants from The National Natural Science Foundation of China (82272631, 82072596, 82173339, 82172766), the National “111” Project (Project #111–2–12), the Hunan Provincial Key Research and Development Program (2022SK2026), the Scientific Research Program of FuRong laboratory(2023SK2094), the Natural Science Foundation of Hunan Province, China (2020JJ4920, 2020JJ4838, 2020JJ4766), the Beijing Xisike Clinical Oncology Research Foundation (Y-HR2020ZD-0052).

Author information

Authors and Affiliations

  1. NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, 410013, China

    Xingxing Lu, Yan Mei, Chunmei Fan, Pan Chen, Zhaoyang Zeng, Guiyuan Li, Wei Xiong & Bo Xiang

  2. The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute and School of Basic Medical Sciences, Central South University, Changsha, 410078, Hunan, China

    Xingxing Lu, Yan Mei, Chunmei Fan, Zhaoyang Zeng, Guiyuan Li, Wei Xiong & Bo Xiang

  3. FuRong Laboratory, Changsha, 410078, Hunan, China

    Xingxing Lu, Yan Mei, Chunmei Fan, Zhaoyang Zeng, Guiyuan Li, Wei Xiong & Bo Xiang

  4. Hunan Key Laboratory of Nonresolving Inflammation and Cancer, The Third Xiangya Hospital, Central South University, Changsha, 410013, Hunan, China

    Xingxing Lu, Yan Mei, Chunmei Fan, Xiayu Li, Zhaoyang Zeng, Guiyuan Li, Wei Xiong & Bo Xiang

  5. Department of Dermatology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China

    Mei Yi

Authors
  1. Xingxing Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yan Mei
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Chunmei Fan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Pan Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Xiayu Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Zhaoyang Zeng
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Guiyuan Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Wei Xiong
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Bo Xiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Mei Yi
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Conception and design: B. Xiang, M. Yi

Development of methodology: X.-X. Lu, Y. Mei, B. Xiang

Acquisition of data (provided animals, acquired and managed patients, provided facilities, etc.): X.-X. Lu, Y. Mei, C.-M. Fan, P. Chen, X.-Y. Li, Z.-Y. Zeng, G.-Y. Li, W. Xiong, B. Xiang, M. Yi

Analysis and interpretation of data (e.g., statistical analysis, biostatistics, computational analysis): X.-X. Lu, Y. Mei, B. Xiang

Writing, review, and/or revision of the manuscript: X.-X. Lu, B. Xiang

Study supervision: B. Xiang, M. Yi

Corresponding authors

Correspondence to Bo Xiang or Mei Yi.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (XLSX 73 KB)

Fig. S1.

The mRNA expression levels of AHNAK in the normal nasopharyngeal epithelium NP69 and NPC cells were determined by RT-PCR (PNG 24 kb)

High resolution image (TIF 374 kb)

Fig. S2.

A, HNE1 cells stably expressing AHNAK shRNA (shRNA/AHNAK) or shRNA (shRNA/Control) were injected into nude mice. Macroscopic and body weight changes of mice after 8 weeks. B, D, F, macroscopic and microscopic representative images of tumors in lung tissue and the average number of metastases per group are shown. C, E, G, macroscopic and microscopic representative images of tumors in liver tissue and the average number of metastases per group are shown (PNG 5806 kb)

High resolution image (TIF 25598 kb)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lu, X., Mei, Y., Fan, C. et al. Silencing AHNAK promotes nasopharyngeal carcinoma progression by upregulating the ANXA2 protein. Cell Oncol. (2023). https://doi.org/10.1007/s13402-023-00898-3

Download citation

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s13402-023-00898-3

Keywords

Search

Navigation