Top

Published in:

01-01-2020 | Original Article

Rab23 Promotes Hepatocellular Carcinoma Cell Migration Via Rac1/TGF-β Signaling

Authors: Li Zhang, Bingqiang Zhang, Wenxian You, Pan Li, Youlin Kuang

Published in: Pathology & Oncology Research | Issue 1/2020

Abstract

Rab23 is a member of Ras-related small GTPase family, which plays a critical role in the progression of wide range of tumors. However, its biological function in hepatocellular carcinoma still remains unclear. Here, we investigated the effects of Rab23 on proliferation and migration in hepatocellular carcinoma cell and its potential mechanisms. We found over-expression of Rab23 promoted the Hep3B hepatocellular carcinoma cell migration, which could be reversed by Rab23 silencing. Rab23 induced Rac1 activation and followed progression of epithelial-mesenchymal transition (EMT) along with upregulation of N-cadherin, snail as well as vimentin and downregulation of E-cadherin via upregulating Transforming Growth Factor-β (TGF-β). Silencing Rac1 significantly attenuated Rab23-induced HepG2 migration and TGF-β. Moreover, knockdown of TGF-β effectively attenuated Rab23-induced EMT. Taken together, we demonstrated a mechanistic cascade of Rab23 enhangcing Rac1 activation and subsequent TGF-β expression, leading to hepatocellular carcinoma cell migration.

Massarweh NN, El-Serag HB (2017) Epidemiology of hepatocellular carcinoma and intrahepatic cholangiocarcinoma. Cancer Control 24:1073274817729245CrossRef

Forner A, Llovet JM, Bruix J (2012) Hepatocellular carcinoma. In: Lancet, vol 379, (London), pp 1245–1255

Delevoye C, Goud B (2015) Rab GTPases and kinesin motors in endosomal trafficking. Methods Cell Biol 130:235–246CrossRef

Eggenschwiler JT, Espinoza E, Anderson KV (2001) Rab23 is an essential negative regulator of the mouse sonic hedgehog signalling pathway. Nature 412:194–198CrossRef

Cai ZZ, Xu LB, Cai JL, Wang JS, Zhou B, Hu H (2015) Inactivation of Rab23 inhibits the invasion and motility of pancreatic duct adenocarcinoma. Genet Mol Res 14:2707–2715CrossRef

Jiang Y, Han Y, Sun C, Han C, Han N, Zhi W, Qiao Q (2016) Rab23 is overexpressed in human bladder cancer and promotes cancer cell proliferation and invasion. Tumour Biol 37:8131–8138CrossRef

Wang M, Dong Q, Wang Y (2016) Rab23 is overexpressed in human astrocytoma and promotes cell migration and invasion through regulation of Rac1. Tumour Biol 37:11049–11055CrossRef

Hou Q, Wu YH, Grabsch H, Zhu Y, Leong SH, Ganesan K, Cross D, Tan LK, Tao J, Gopalakrishnan V, Tang BL, Kon OL, Tan P (2008) Integrative genomics identifies RAB23 as an invasion mediator gene in diffuse-type gastric cancer. Cancer Res 68:4623–4630CrossRef

Denning KM, Smyth PC, Cahill SF, Finn SP, Conlon E, Li J, Flavin RJ, Aherne ST, Guenther SM, Ferlinz A, O'Leary JJ, Sheils OM (2007) A molecular expression signature distinguishing follicular lesions in thyroid carcinoma using preamplification RT-PCR in archival samples. Mod Pathol 20:1095–1102CrossRef

10.

Liu YJ, Wang Q, Li W, Huang XH, Zhen MC, Huang SH, Chen LZ, Xue L, Zhang HW (2007) Rab23 is a potential biological target for treating hepatocellular carcinoma. World J Gastroenterol 13:1010–1017CrossRef

11.

Jansen S, Gosens R, Wieland T, Schmidt M (2017) Paving the rho in cancer metastasis: rho GTPases and beyond. Pharmacol Ther

12.

Bid HK, Roberts RD, Manchanda PK, Houghton PJ (2013) RAC1: an emerging therapeutic option for targeting cancer angiogenesis and metastasis. Mol Cancer Ther 12:1925–1934CrossRef

13.

Melzer C, Hass R, von der Ohe J, Lehnert H, Ungefroren H (2017) The role of TGF-beta and its crosstalk with RAC1/RAC1b signaling in breast and pancreas carcinoma. Cell Commun Signal 15:19CrossRef

14.

Liu Y, Zeng C, Bao N, Zhao J, Hu Y, Li C, Chi S (2015) Effect of Rab23 on the proliferation and apoptosis in breast cancer. Oncol Rep 34:1835–1844CrossRef

15.

Cheng L, Yang F, Zhou B, Yang H, Yuan Y, Li X, Han S (2016) RAB23, regulated by miR-92b, promotes the progression of esophageal squamous cell carcinoma. Gene 595:31–38CrossRef

16.

Jian Q, Miao Y, Tang L, Huang M, Yang Y, Ba W, Liu Y, Chi S, Li C (2016) Rab23 promotes squamous cell carcinoma cell migration and invasion via integrin beta1/Rac1 pathway. Oncotarget 7:5342–5352PubMed

17.

Zhang XY, Mu JH, Liu LY, Zhang HZ (2017) Upregulation of miR-802 suppresses gastric cancer oncogenicity via targeting RAB23 expression. Eur Rev Med Pharmacol Sci 21:4071–4078PubMed

18.

Dong C, Du Q, Wang Z, Wang Y, Wu S, Wang A (2016) MicroRNA-665 suppressed the invasion and metastasis of osteosarcoma by directly inhibiting RAB23. Am J Transl Res 8:4975–4981PubMedPubMedCentral

19.

Katz LH, Li Y, Chen JS, Munoz NM, Majumdar A, Chen J, Mishra L (2013) Targeting TGF-beta signaling in cancer. Expert Opin Ther Targets 17:743–760CrossRef

20.

Mishra L, Banker T, Murray J, Byers S, Thenappan A, He AR, Shetty K, Johnson L, Reddy EP (2009) Liver stem cells and hepatocellular carcinoma. Hepatology (Baltimore, MD) 49:318–329CrossRef

21.

Meindl-Beinker NM, Matsuzaki K, Dooley S (2012) TGF-beta signaling in onset and progression of hepatocellular carcinoma. In: Digestive Diseases, vol 30, (Basel), pp 514–523

22.

Wendt MK, Tian M, Schiemann WP (2012) Deconstructing the mechanisms and consequences of TGF-beta-induced EMT during cancer progression. Cell Tissue Res 347:85–101CrossRef

23.

Caja L, Bertran E, Campbell J, Fausto N, Fabregat I (2011) The transforming growth factor-beta (TGF-beta) mediates acquisition of a mesenchymal stem cell-like phenotype in human liver cells. J Cell Physiol 226:1214–1223CrossRef

Title: Rab23 Promotes Hepatocellular Carcinoma Cell Migration Via Rac1/TGF-β Signaling
Authors: Li Zhang
Bingqiang Zhang
Wenxian You
Pan Li
Youlin Kuang
Publication date: 01-01-2020
Publisher: Springer Netherlands
Published in: Pathology & Oncology Research / Issue 1/2020
Print ISSN: 1219-4956
Electronic ISSN: 1532-2807
DOI: https://doi.org/10.1007/s12253-018-0463-z

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1/2020

Targeted Mutational Profiling and a Powerful Risk Score as Additional Tools for the Diagnosis of Papillary Thyroid Cancer

KIT Mutation Incidence and Pattern of Melanoma in Central Europe

25th Anniversary of Pathology Oncology Research

Miki (Mitotic Kinetics Regulator) Immunoexpression in Normal Liver, Cirrhotic Areas and Hepatocellular Carcinomas: a Preliminary Study with Clinical Relevance

The Role of Log Odds of Positive Lymph Nodes in Predicting the Survival after Resection for Ampullary Adenocarcinoma

Atorvastatin and Caffeine in Combination Regulates Apoptosis, Migration, Invasion and Tumorspheres of Prostate Cancer Cells

Keynote webinar | Spotlight on antibody–drug conjugates in cancer