Anillin Interacts with RhoA to Promote Tumor Progression in Anaplastic Thyroid Cancer by Activating the PI3K/AKT Pathway

Overview

Journal Endocrine

Specialty Endocrinology

Date 2024 Dec 31

PMID 39738892

Authors

Shi-Tong Yu

Bai-Hui Sun

Jun-Na Ge

Zhi-Gang Wei

Zhi-Cheng Zhang

Wei-Sheng Chen

Ting-Ting Li

Shang-Tong Lei

Affiliations

Soon will be listed here.

Abstract

Background: Anaplastic thyroid cancer (ATC) is the most aggressive thyroid malignancy and has an extremely poor prognosis, necessitating novel therapeutic strategies. This study investigated the role of anillin (ANLN) in ATC, focusing on its impact on tumor growth and metastasis through the RhoA/PI3K/AKT signaling pathway.

Methods: TCGA and GEO datasets were analyzed to identify key molecular alterations in thyroid cancer. ANLN expression was assessed in clinical samples. Functional assays, including CCK-8, colony formation, scratch, and Transwell invasion assays, and mouse xenograft models, were conducted to evaluate the biological role of ANLN. Coimmunoprecipitation, immunofluorescence, and active Rho GTPase pull-down assays, as well as phosphorylation antibody arrays, were used to explore the underlying mechanisms.

Results: Analysis of TCGA and GEO datasets revealed that ANLN is upregulated in thyroid cancers, including ATC and PTC, with higher ANLN expression correlating with worse survival outcomes. Functional studies demonstrated that ANLN promoted ATC cell proliferation, migration, and invasion. In vivo, ANLN knockdown inhibited tumor growth in xenograft models. Mechanistically, ANLN directly interacted with RhoA, facilitating its activation and subsequent stimulation of the PI3K/AKT signaling pathway. The tumorigenic effects of ANLN were suppressed by AKT inhibition with afuresertib or RhoA silencing.

Conclusion: ANLN plays a crucial role in ATC progression by activating the RhoA/PI3K/AKT pathway, suggesting its potential as a therapeutic target in ATC.

Citing Articles

Unveiling novel susceptibility genes and drug targets for basal cell carcinoma by a cross-tissue transcriptome-wide association study.

Sun H, Li L, Xin X, Yan J, Huang T Discov Oncol. 2025; 16(1):288.

PMID: 40063313 PMC: 11893943. DOI: 10.1007/s12672-025-02019-y.

References

Ferrari S, Elia G, Ragusa F, Ruffilli I, La Motta C, Paparo S . Novel treatments for anaplastic thyroid carcinoma. Gland Surg. 2020; 9(Suppl 1):S28-S42. PMC: 6995904. DOI: 10.21037/gs.2019.10.18. View

Han B, Zheng R, Zeng H, Wang S, Sun K, Chen R . Cancer incidence and mortality in China, 2022. J Natl Cancer Cent. 2024; 4(1):47-53. PMC: 11256708. DOI: 10.1016/j.jncc.2024.01.006. View

Boucai L, Zafereo M, Cabanillas M . Thyroid Cancer: A Review. JAMA. 2024; 331(5):425-435. DOI: 10.1001/jama.2023.26348. View

Haugen B, Alexander E, Bible K, Doherty G, Mandel S, Nikiforov Y . 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid. 2015; 26(1):1-133. PMC: 4739132. DOI: 10.1089/thy.2015.0020. View

Bible K, Kebebew E, Brierley J, Brito J, Cabanillas M, Clark Jr T . 2021 American Thyroid Association Guidelines for Management of Patients with Anaplastic Thyroid Cancer. Thyroid. 2021; 31(3):337-386. PMC: 8349723. DOI: 10.1089/thy.2020.0944. View

Naydenov N, Koblinski J, Ivanov A . Anillin is an emerging regulator of tumorigenesis, acting as a cortical cytoskeletal scaffold and a nuclear modulator of cancer cell differentiation. Cell Mol Life Sci. 2020; 78(2):621-633. PMC: 11072349. DOI: 10.1007/s00018-020-03605-9. View

Budnar S, Husain K, Gomez G, Naghibosadat M, Varma A, Verma S . Anillin Promotes Cell Contractility by Cyclic Resetting of RhoA Residence Kinetics. Dev Cell. 2019; 49(6):894-906.e12. DOI: 10.1016/j.devcel.2019.04.031. View

Oegema K, Savoian M, Mitchison T, Field C . Functional analysis of a human homologue of the Drosophila actin binding protein anillin suggests a role in cytokinesis. J Cell Biol. 2000; 150(3):539-52. PMC: 2175195. DOI: 10.1083/jcb.150.3.539. View

Suzuki C, Daigo Y, Ishikawa N, Kato T, Hayama S, Ito T . ANLN plays a critical role in human lung carcinogenesis through the activation of RHOA and by involvement in the phosphoinositide 3-kinase/AKT pathway. Cancer Res. 2005; 65(24):11314-25. DOI: 10.1158/0008-5472.CAN-05-1507. View

10.

Zhou W, Wang Z, Shen N, Pi W, Jiang W, Huang J . Knockdown of ANLN by lentivirus inhibits cell growth and migration in human breast cancer. Mol Cell Biochem. 2014; 398(1-2):11-9. DOI: 10.1007/s11010-014-2200-6. View

11.

Lian Y, Huang Y, Wang J, Deng M, Xia T, Zeng M . Anillin is required for tumor growth and regulated by miR-15a/miR-16-1 in HBV-related hepatocellular carcinoma. Aging (Albany NY). 2018; 10(8):1884-1901. PMC: 6128427. DOI: 10.18632/aging.101510. View

12.

Wang A, Dai H, Gong Y, Zhang C, Shu J, Luo Y . ANLN-induced EZH2 upregulation promotes pancreatic cancer progression by mediating miR-218-5p/LASP1 signaling axis. J Exp Clin Cancer Res. 2019; 38(1):347. PMC: 6686567. DOI: 10.1186/s13046-019-1340-7. View

13.

Weinberger P, Raju Ponny S, Xu H, Bai S, Smallridge R, Copland J . Cell Cycle M-Phase Genes Are Highly Upregulated in Anaplastic Thyroid Carcinoma. Thyroid. 2016; 27(2):236-252. PMC: 5314727. DOI: 10.1089/thy.2016.0285. View

14.

Lessey E, Guilluy C, Burridge K . From mechanical force to RhoA activation. Biochemistry. 2012; 51(38):7420-32. PMC: 3567302. DOI: 10.1021/bi300758e. View

15.

Brooks E, Galarza S, Gencoglu M, Cornelison R, Munson J, Peyton S . Applicability of drug response metrics for cancer studies using biomaterials. Philos Trans R Soc Lond B Biol Sci. 2019; 374(1779):20180226. PMC: 6627013. DOI: 10.1098/rstb.2018.0226. View

16.

Zhong W, Hsu S, Ho P, Liang Y, Chang T, Lee W . Lovastatin inhibits proliferation of anaplastic thyroid cancer cells through up-regulation of p27 by interfering with the Rho/ROCK-mediated pathway. Biochem Pharmacol. 2011; 82(11):1663-72. DOI: 10.1016/j.bcp.2011.08.021. View

17.

Zhong W, Tsai Y, Chin L, Tseng J, Tang L, Horng S . A Synergistic Anti-Cancer Effect of Troglitazone and Lovastatin in a Human Anaplastic Thyroid Cancer Cell Line and in a Mouse Xenograft Model. Int J Mol Sci. 2018; 19(7). PMC: 6073567. DOI: 10.3390/ijms19071834. View

18.

Wang F, Xiang Z, Huang T, Zhang M, Zhou W . ANLN Directly Interacts with RhoA to Promote Doxorubicin Resistance in Breast Cancer Cells. Cancer Manag Res. 2020; 12:9725-9734. PMC: 7548225. DOI: 10.2147/CMAR.S261828. View

19.

Chen J, Li Z, Jia X, Song W, Wu H, Zhu H . Targeting anillin inhibits tumorigenesis and tumor growth in hepatocellular carcinoma via impairing cytokinesis fidelity. Oncogene. 2022; 41(22):3118-3130. DOI: 10.1038/s41388-022-02274-1. View

20.

Yu S, Zhong Q, Chen R, Han P, Li S, Zhang H . CRLF1 promotes malignant phenotypes of papillary thyroid carcinoma by activating the MAPK/ERK and PI3K/AKT pathways. Cell Death Dis. 2018; 9(3):371. PMC: 5841418. DOI: 10.1038/s41419-018-0352-0. View