Histone deacetylase 6 and cytoplasmic linker protein 170 function together to regulate the motility of pancreatic cancer cells
Received date: 17 Oct 2013
Accepted date: 05 Nov 2013
Published date: 23 Jun 2014
Copyright
Pancreatic cancer is a devastating disease with the worst prognosis among all the major human malignancies. The propensity to rapidly metastasize contributes significantly to the highly aggressive feature of pancreatic cancer. The molecular mechanisms underlying this remain elusive, and proteins involved in the control of pancreatic cancer cell motility are not fully characterized. In this study, we find that histone deacetylase 6 (HDAC6), a member of the class II HDAC family, is highly expressed at both protein and mRNA levels in human pancreatic cancer tissues. HDAC6 does not obviously affect pancreatic cancer cell proliferation or cell cycle progression. Instead, it significantly promotes the motility of pancreatic cancer cells. Further studies reveal that HDAC6 interacts with cytoplasmic linker protein 170 (CLIP-170) and that these two proteins function together to stimulate the migration of pancreatic cancer cells. These findings provide mechanistic insight into the progression of pancreatic cancer and suggest HDAC6 as a potential target for the management of this malignancy.
Key words: pancreatic cancer; cell motility; cell migration; cell proliferation; cell cycle
Dengwen Li , Xiaodong Sun , Linlin Zhang , Bing Yan , Songbo Xie , Ruming Liu , Min Liu , Jun Zhou . Histone deacetylase 6 and cytoplasmic linker protein 170 function together to regulate the motility of pancreatic cancer cells[J]. Protein & Cell, 2014 , 5(3) : 214 -223 . DOI: 10.1007/s13238-013-0010-3
1 |
Aldana-Masangkay GI, Sakamoto KM (2011) The role of HDAC6 in cancer. J Biomed Biotechnol2011: 875824
|
2 |
Amos LA, Schlieper D (2005) Microtubules and maps. Adv Protein Chem71: 257-298
|
3 |
Berridge MV, Herst PM, Tan AS (2005) Tetrazolium dyes as tools in cell biology: new insights into their cellular reduction. Biotechnol Annu<?Pub Caret?> Rev11: 127-152
|
4 |
Dallavalle S, Pisano C, Zunino F (2012) Development and therapeutic impact of HDAC6-selective inhibitors. Biochem Pharmacol84: 756-765
|
5 |
Dragestein KA, van Cappellen WA, van Haren J, Tsibidis GD, Akhmanova A, Knoch TA, Grosveld F, Galjart N (2008) Dynamic behavior of GFP-CLIP-170 reveals fast protein turnover on microtubule plus ends. J Cell Biol180: 729-737
|
6 |
Etienne-Manneville S (2008) Polarity proteins in migration and invasion. Oncogene27: 6970-6980
|
7 |
Ghaneh P, Costello E, Neoptolemos JP (2008) Biology and management of pancreatic cancer. Postgrad Med J84: 478-497
|
8 |
Haggarty SJ, Koeller KM, Wong JC, Grozinger CM, Schreiber SL (2003) Domain-selective small-molecule inhibitor of histone deacetylase 6 (HDAC6)-mediated tubulin deacetylation. Proc Natl Acad Sci USA100: 4389-4394
|
9 |
Hezel AF, Kimmelman AC, Stanger BZ, Bardeesy N, Depinho RA (2006) Genetics and biology of pancreatic ductal adenocarcinoma. Genes Dev20: 1218-1249
|
10 |
Hubbert C, Guardiola A, Shao R, Kawaguchi Y, Ito A, Nixon A, Yoshida M, Wang XF, Yao TP (2002) HDAC6 is a microtubuleassociated deacetylase. Nature417: 455-458
|
11 |
Huo L, Li D, Sun X, Shi X, Karna P, Yang W, Liu M, Qiao W, Aneja R, Zhou J (2011) Regulation of Tat acetylation and transactivation activity by the microtubule-associated deacetylase HDAC6. J Biol Chem286: 9280-9286
|
12 |
Kovacs JJ, Murphy PJ, Gaillard S, Zhao X, Wu JT, Nicchitta CV, Yoshida M, Toft DO, Pratt WB, Yao TP (2005) HDAC6 regulates Hsp90 acetylation and chaperone-dependent activation of glucocorticoid receptor. Mol Cell18: 601-607
|
13 |
Li H, Liu XS, Yang X, Wang Y, Turner JR, Liu X (2010) Phosphorylation of CLIP-170 by Plk1 and CK2 promotes timely formation of kinetochore-microtubule attachments. EMBO J29: 2953-2965
|
14 |
Li D, Xie S, Ren Y, Huo L, Gao J, Cui D, Liu M, Zhou J (2011) Microtubule-associated deacetylase HDAC6 promotes angiogenesis by regulating cell migration in an EB1-dependent manner. Protein Cell2: 150-160
|
15 |
Lindemann RK, Gabrielli B, Johnstone RW (2004) Histone-deacetylase inhibitors for the treatment of cancer. Cell Cycle3: 779-788
|
16 |
Maekawa H, Schiebel E (2004) CLIP-170 family members: a motordriven ride to microtubule plus ends. Dev Cell6: 746-748
|
17 |
Matsuyama A, Shimazu T, Sumida Y, Saito A, Yoshimatsu Y, Seigneurin-Berny D, Osada H, Komatsu Y, Nishino N, Khochbin S
|
18 |
Nakano A, Kato H, Watanabe T, Min KD, Yamazaki S, Asano Y, Seguchi O, Higo S, Shintani Y, Asanuma H
|
19 |
Olson MF, Sahai E (2009) The actin cytoskeleton in cancer cell motility. Clin Exp Metastasis26: 273-287
|
20 |
Parmigiani RB, Xu WS, Venta-Perez G, Erdjument-Bromage H, Yaneva M, Tempst P, Marks PA (2008) HDAC6 is a specific deacetylase of peroxiredoxins and is involved in redox regulation. Proc Natl Acad Sci USA105: 9633-9638
|
21 |
Pierre P, Scheel J, Rickard JE, Kreis TE (1992) CLIP-170 links endocytic vesicles to microtubules. Cell70: 887-900
|
22 |
Rodriguez OC, Schaefer AW, Mandato CA, Forscher P, Bement WM, Waterman-Storer CM (2003) Conserved microtubule-actin interactions in cell movement and morphogenesis. Nat Cell Biol5: 599-609
|
23 |
Shi X, Liu M, Li D, Wang J, Aneja R, Zhou J (2012) Cep70 contributes to angiogenesis by modulating microtubule rearrangement and stimulating cell polarization and migration. Cell Cycle11: 1554-1563
|
24 |
Sun X, Li D, Yang Y, Ren Y, Li J, Wang Z, Dong B, Liu M, Zhou J (2012) Microtubule-binding protein CLIP-170 is a mediator of paclitaxel sensitivity. J Pathol226: 666-673
|
25 |
Sun X, Li F, Dong B, Suo S, Liu M, Li D, Zhou J (2013a) Regulation of tumor angiogenesis by the microtubule-binding protein CLIP-170. Protein Cell4: 266-276
|
26 |
Sun X, Liu M, Hao J, Li D, Luo Y, Wang X, Yang Y, Li F, Shui W, Chen Q
|
27 |
Takashima S (2011) AMP-kinase regulates the speed of microtubule polymerization and cell polarity by phosphorylation of microtubule plus end protein CLIP-170. Seikagaku J Jpn Biochem Soc83: 850-854
|
28 |
Valenzuela-Fernandez A, Cabrero JR, Serrador JM, Sanchez-Madrid F (2008) HDAC6: a key regulator of cytoskeleton, cell migration and cell-cell interactions. Trends Cell Biol18: 291-297
|
29 |
Vichai V, Kirtikara K (2006) Sulforhodamine B colorimetric assay for cytotoxicity screening. Nat Protoc1: 1112-1116
|
30 |
Waterman-Storer CM, Salmon E (1999) Positive feedback interactions between microtubule and actin dynamics during cell motility. Curr Opin Cell Biol11: 61-67
|
31 |
Wells A, Grahovac J, Wheeler S, Ma B, Lauffenburger D (2013) Targeting tumor cell motility as a strategy against invasion and metastasis. Trends Pharmacol Sci34: 283-289
|
32 |
Yang X, Li H, Liu XS, Deng A, Liu X (2009) Cdc2-mediated phosphorylation of CLIP-170 is essential for its inhibition of centrosome reduplication. J Biol Chem284: 28775-28782
|
33 |
Zhang Y, Li N, Caron C, Matthias G, Hess D, Khochbin S, Matthias P (2003) HDAC-6 interacts with and deacetylates tubulin and microtubules in vivo. EMBO J22: 1168-1179
|
34 |
Zhang X, Yuan Z, Zhang Y, Yong S, Salas-Burgos A, Koomen J, Olashaw N, Parsons JT, Yang XJ, Dent SR
|
35 |
Zhou J, Vos CC, Gjyrezi A, Yoshida M, Khuri FR, Tamanoi F, Giannakakou P (2009) The protein farnesyl transferase regulates HDAC6 activity in a microtubule-dependent manner. J Biol Chem284: 9648-9655
|
/
〈 | 〉 |