Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Cancer Cell International
Published in: Cancer Cell International 1/2015

Open Access 01-12-2015 | Primary research

Transient knockdown-mediated deficiency in plectin alters hepatocellular motility in association with activated FAK and Rac1-GTPase

Authors: Chiung-Chi Cheng, Yen-Chang Clark Lai, Yih-Shyong Lai, Yung-Hsiang Hsu, Wei-Ting Chao, Kee-Chin Sia, Yu-Hui Tseng, Yi-Hsiang Liu

Published in: Cancer Cell International | Issue 1/2015

Login to get access

Abstract

Background

Plectin is one of the cytolinker proteins that play a crucial role in maintaining the integrity of cellular architecture. It is a component of desmosome complexes connecting cytoskeletal proteins and trans-membrane molecules. In epithelial cells, plectin connects cytokeratins and integrin α6β4 in hemidesmosomes anchoring to the extracellular matrix. In addition to the function of molecular adherent, plectin has been reported to exhibit functions affecting cellular signals and responsive activities mediated by stress, cellular migration, polarization as well as the dynamic movement of actin filaments. Plectin deficiency in hepatocellular carcinoma results in abnormal expression of cytokeratin 18 and disassembled hemidesmosome. Therefore, it is hypothesized that the plectin deficiency-mediated collapse of cytoskeleton may modulate cellular motility that is associated with consequent metastatic behaviors of cancer cells.

Methods and results

The cellular motility of plectin-deficient Chang liver cells generated by transient knockdown were analyzed by trans-well migration assay and the results revealed a higher migration rate. The confocal microscopy also demonstrated less organized and more polarized morphology as well as more focal adhesion kinase activity in comparison with that of the mock Chang liver cells. Furthermore, plectin-knockdown in Chang liver cells was associated with a higher activity of Rac1-GTPase in accordance with the results of the Rac1 pull-down assay. The immunohistochemical assay on human hepatocellular carcinoma showed that the expression of focal adhesion kinase was increased in the invasive front of tumor.

Conclusion

Plectin-deficient human hepatic cells exhibit higher cell motility associated with increase in focal adhesion kinase activity that are comparable to the properties of invasive hepatocellular carcinoma.
Literature
1.
Wiche G. Role of plectin in cytoskeleton organization and dynamics. J Cell Sci. 1998;111(Pt 17):2477–86.PubMed
2.
Burgstaller G, Gregor M, Winter L, Wiche G. Keeping the vimentin network under control: cell-matrix adhesion-associated plectin 1f affects cell shape and polarity of fibroblasts. Mol Biol Cell. 2010;21(19):3362–75.CrossRefPubMedCentralPubMed
3.
Osmanagic-Myers S, Wiche G. Plectin-RACK1 (receptor for activated C kinase 1) scaffolding: a novel mechanism to regulate protein kinase C activity. J Biol Chem. 2004;279(18):18701–10.CrossRefPubMed
4.
Andrä K, Nikolic B, Stocher M, Drenckhahn D, Wiche G. Not just scaffolding: plectin regulates actin dynamics in cultured cells. Genes Dev. 1998;12(21):3442–51.CrossRefPubMedCentralPubMed
5.
Osmanagic-Myers S, Gregor M, Walko G, Burgstaller G, Reipert S, Wiche G. Plectin-controlled keratin cytoarchitecture affects MAP kinases involved in cellular stress response and migration. J Cell Biol. 2006;174(4):557–68.CrossRefPubMedCentralPubMed
6.
Elliott CE, Becker B, Oehler S, Castanon MJ, Hauptmann R, Wiche G. Plectin transcript diversity: identification and tissue distribution of variants with distinct first coding exons and rodless isoforms. Genomics. 1997;42(1):115–25.CrossRefPubMed
7.
Garcia-Alvarez B, Bobkov A, Sonnenberg A, de Pereda JM. Structural and functional analysis of the actin binding domain of plectin suggests alternative mechanisms for binding to F-actin and integrin beta4. Structure. 2003;11(6):615–25.CrossRefPubMed
8.
Sevcik J, Urbanikova L, Kost’an J, Janda L, Wiche G. Actin-binding domain of mouse plectin. Crystal structure and binding to vimentin. Eur J Biochem. 2004;271(10):1873–84.CrossRefPubMed
9.
Rezniczek GA, de Pereda JM, Reipert S, Wiche G. Linking integrin alpha6beta4-based cell adhesion to the intermediate filament cytoskeleton: direct interaction between the beta4 subunit and plectin at multiple molecular sites. J Cell Biol. 1998;141(1):209–25.CrossRefPubMedCentralPubMed
10.
Kostan J, Gregor M, Walko G, Wiche G. Plectin isoform-dependent regulation of keratin-integrin alpha6beta4 anchorage via Ca2+/calmodulin. J Biol Chem. 2009;284(27):18525–36.CrossRefPubMedCentralPubMed
11.
Mierke CT. The role of focal adhesion kinase in the regulation of cellular mechanical properties. Phys Biol. 2013;10(6):065005.CrossRefPubMed
12.
13.
Lightfoot Jr HM, Lark A, Livasy CA, Moore DT, Cowan D, Dressler L, et al. Upregulation of focal adhesion kinase (FAK) expression in ductal carcinoma in situ (DCIS) is an early event in breast tumorigenesis. Breast Cancer Res Treat. 2004;88(2):109–16.CrossRefPubMed
14.
Oktay MH, Oktay K, Hamele-Bena D, Buyuk A, Koss LG. Focal adhesion kinase as a marker of malignant phenotype in breast and cervical carcinomas. Hum Pathol. 2003;34(3):240–5.CrossRefPubMed
15.
16.
Cheng CC, Liu YH, Ho CC, Chao WT, Pei RJ, Hsu YH, et al. The influence of plectin deficiency on stability of cytokeratin18 in hepatocellular carcinoma. J Mol Histol. 2008;39(2):209–16.CrossRefPubMed
17.
Liu YH, Cheng CC, Ho CC, Chao WT, Pei RJ, Hsu YH, et al. Plectin deficiency on cytoskeletal disorganization and transformation of human liver cells in vitro. Med Mol Morphol. 2011;44(1):21–6.CrossRefPubMed
18.
Roessler S, Long EL, Budhu A, Chen Y, Zhao X, Ji J, et al. Integrative genomic identification of genes on 8p associated with hepatocellular carcinoma progression and patient survival. Gastroenterology. 2012;142(4):957–66. e912.CrossRefPubMedCentralPubMed
19.
Legate KR, Wickstrom SA, Fassler R. Genetic and cell biological analysis of integrin outside-in signaling. Genes Dev. 2009;23(4):397–418.CrossRefPubMed
20.
Hehlgans S, Haase M, Cordes N. Signalling via integrins: implications for cell survival and anticancer strategies. Biochim Biophys Acta. 2007;1775(1):163–80.PubMed
21.
Webb DJ, Parsons JT, Horwitz AF. Adhesion assembly, disassembly and turnover in migrating cells – over and over and over again. Nat Cell Biol. 2002;4(4):E97–100.CrossRefPubMed
22.
Fraley SI, Feng Y, Krishnamurthy R, Kim DH, Celedon A, Longmore GD, et al. A distinctive role for focal adhesion proteins in three-dimensional cell motility. Nat Cell Biol. 2010;12(6):598–604.CrossRefPubMedCentralPubMed
23.
Ridley AJ. Rho GTPases and actin dynamics in membrane protrusions and vesicle trafficking. Trends Cell Biol. 2006;16(10):522–9.CrossRefPubMed
24.
Suetsugu S, Miki H, Takenawa T. Spatial and temporal regulation of actin polymerization for cytoskeleton formation through Arp2/3 complex and WASP/WAVE proteins. Cell Motil Cytoskeleton. 2002;51(3):113–22.CrossRefPubMed
Metadata
Title
Transient knockdown-mediated deficiency in plectin alters hepatocellular motility in association with activated FAK and Rac1-GTPase
Authors
Chiung-Chi Cheng
Yen-Chang Clark Lai
Yih-Shyong Lai
Yung-Hsiang Hsu
Wei-Ting Chao
Kee-Chin Sia
Yu-Hui Tseng
Yi-Hsiang Liu
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2015
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-015-0177-1

Other articles of this Issue 1/2015

Cancer Cell International 1/2015 Go to the issue

Review

Cyclooxygeanse-2 promotes metastasis in osteosarcoma

Primary research

PBK/TOPK mediates geranylgeranylation signaling for breast cancer cell proliferation

Primary research

GSK3β mediates pancreatic cancer cell invasion in vitro via the CXCR4/MMP-2 Pathway

Primary research

The effect of nilotinib plus arsenic trioxide on the proliferation and differentiation of primary leukemic cells from patients with chronic myoloid leukemia in blast crisis

Review

Understanding the colon cancer stem cells and perspectives on treatment

Review

MicroRNA-7: a promising new target in cancer therapy
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
Image Credits