Please use this identifier to cite or link to this item:
Study of protein complex formation between a novel tumor suppressor HLJ1 and beta-actin on human lung adenocarcinoma migration and invasion
|關鍵字:||熱休克蛋白;heat shock protein;肌動蛋白;actin||出版社:||分子生物學研究所||引用:||參考文獻 Adamson, P., Etienne, S., Couraud, P.O., Calder, V. and Greenwood, J. (1999) Lymphocyte migration through brain endothelial cell monolayers involves signaling through endothelial ICAM-1 via a rho-dependent pathway. J Immunol, 162, 2964-2973. Akyol, S., Gercel-Taylor, C., Reynolds, L.C. and Taylor, D.D. (2006) HSP-10 in ovarian cancer: expression and suppression of T-cell signaling. Gynecol Oncol, 101, 481-486. Albelda, S.M. (1993) Role of integrins and other cell adhesion molecules in tumor progression and metastasis. Lab Invest, 68, 4-17. Banerjea, A., Feakins, R.M., Nickols, C.D., Phillips, S.M., Powar, M.P., Bustin, S.A. and Dorudi, S. (2005) Immunogenic hsp-70 is overexpressed in colorectal cancers with high-degree microsatellite instability. Dis Colon Rectum, 48, 2322-2328. Barnes, J.A., Dix, D.J., Collins, B.W., Luft, C. and Allen, J.W. (2001) Expression of inducible Hsp70 enhances the proliferation of MCF-7 breast cancer cells and protects against the cytotoxic effects of hyperthermia. Cell Stress Chaperones, 6, 316-325. Benndorf, R., Hayess, K., Ryazantsev, S., Wieske, M., Behlke, J. and Lutsch, G. (1994) Phosphorylation and supramolecular organization of murine small heat shock protein HSP25 abolish its actin polymerization-inhibiting activity. J Biol Chem, 269, 20780-20784. Birchmeier, C., Birchmeier, W. and Brand-Saberi, B. (1996) Epithelial-mesenchymal transitions in cancer progression. Acta Anat (Basel), 156, 217-226. Braga, V.M., Betson, M., Li, X. and Lamarche-Vane, N. (2000) Activation of the small GTPase Rac is sufficient to disrupt cadherin-dependent cell-cell adhesion in normal human keratinocytes. Mol Biol Cell, 11, 3703-3721. Bubb, M.R. (2003) Thymosin beta 4 interactions. Vitam Horm, 66, 297-316. Burridge, K. and Fath, K. (1989) Focal contacts: transmembrane links between the extracellular matrix and the cytoskeleton. Bioessays, 10, 104-108. Calderwood, S.K., Khaleque, M.A., Sawyer, D.B. and Ciocca, D.R. (2006) Heat shock proteins in cancer: chaperones of tumorigenesis. Trends Biochem Sci, 31, 164-172. Chen, J.J., Peck, K., Hong, T.M., Yang, S.C., Sher, Y.P., Shih, J.Y., Wu, R., Cheng, J.L., Roffler, S.R., Wu, C.W. and Yang, P.C. (2001) Global analysis of gene expression in invasion by a lung cancer model. Cancer Res, 61, 5223-5230. Cooper, J.A. and Schafer, D.A. (2000) Control of actin assembly and disassembly at filament ends. Curr Opin Cell Biol, 12, 97-103. Crosbie, R.H., Miller, C., Cheung, P., Goodnight, T., Muhlrad, A. and Reisler, E. (1994) Structural connectivity in actin: effect of C-terminal modifications on the properties of actin. Biophys J, 67, 1957-1964. Dai, C. and Whitesell, L. (2005) HSP90: a rising star on the horizon of anticancer targets. Future Oncol, 1, 529-540. Doi, Y.K., Banba, M. and Vertut-Doi, A. (1991) Cysteine-374 of actin resides at the gelsolin contact site in the EGTA-resistant actin-gelsolin complex. Biochemistry, 30, 5769-5777. Fajmut, A., Dobovisek, A. and Brumen, M. (2005) Mathematical modeling of the relation between myosin phosphorylation and stress development in smooth muscles. J Chem Inf Model, 45, 1610-1615. Fischer, R.S. and Fowler, V.M. (2003) Tropomodulins: life at the slow end. Trends Cell Biol, 13, 593-601. Franke, W.W. (2004) Actin''s many actions start at the genes. Nat Cell Biol, 6, 1013-1014. Furukawa, R. and Fechheimer, M. (1997) The structure, function, and assembly of actin filament bundles. Int Rev Cytol, 175, 29-90. Gabai, V.L., Meriin, A.B., Mosser, D.D., Caron, A.W., Rits, S., Shifrin, V.I. and Sherman, M.Y. (1997) Hsp70 prevents activation of stress kinases. A novel pathway of cellular thermotolerance. J Biol Chem, 272, 18033-18037. Gabai, V.L. and Sherman, M.Y. (2002) Invited review: Interplay between molecular chaperones and signaling pathways in survival of heat shock. J Appl Physiol, 92, 1743-1748. Garrido, C., Schmitt, E., Cande, C., Vahsen, N., Parcellier, A. and Kroemer, G. (2003) HSP27 and HSP70: potentially oncogenic apoptosis inhibitors. Cell Cycle, 2, 579-584. Georgopoulos, C. and Welch, W.J. (1993) Role of the major heat shock proteins as molecular chaperones. Annu Rev Cell Biol, 9, 601-634. Guilford, P. (1999) E-cadherin downregulation in cancer: fuel on the fire? Mol Med Today, 5, 172-177. Guo, W. and Giancotti, F.G. (2004) Integrin signalling during tumour progression. Nat Rev Mol Cell Biol, 5, 816-826. Hall, A. (1998) Rho GTPases and the actin cytoskeleton. Science, 279, 509-514. Hanahan, D. and Weinberg, R.A. (2000) The hallmarks of cancer. Cell, 100, 57-70. Hasegawa, T., Xiao, H., Hamajima, F. and Isobe, K. (2000) Interaction between DNA-damage protein GADD34 and a new member of the Hsp40 family of heat shock proteins that is induced by a DNA-damaging reagent. Biochem J, 352 Pt 3, 795-800. Hattori, A., Soga, N., Mito, M., Koike, T. and Shibata, A. (1992) Stress platelets in normal individuals and patients with idiopathic thrombocytopenic purpura. Blood Cells, 18, 281-294. Herman, I.M. (1993) Actin isoforms. Curr Opin Cell Biol, 5, 48-55. Hoe, K.L., Won, M., Chung, K.S., Jang, Y.J., Lee, S.B., Kim, D.U., Lee, J.W., Yun, J.H. and Yoo, H.S. (1998) Isolation of a new member of DnaJ-like heat shock protein 40 (Hsp40) from human liver. Biochim Biophys Acta, 1383, 4-8. Hoffman, P.C., Mauer, A.M. and Vokes, E.E. (2000) Lung cancer. Lancet, 355, 479-485. Huot, J., Houle, F., Spitz, D.R. and Landry, J. (1996) HSP27 phosphorylation-mediated resistance against actin fragmentation and cell death induced by oxidative stress. Cancer Res, 56, 273-279. Jaattela, M. (1993) Overexpression of major heat shock protein hsp70 inhibits tumor necrosis factor-induced activation of phospholipase A2. J Immunol, 151, 4286-4294. Jaattela, M., Wissing, D., Kokholm, K., Kallunki, T. and Egeblad, M. (1998) Hsp70 exerts its anti-apoptotic function downstream of caspase-3-like proteases. Embo J, 17, 6124-6134. Jiang, W.G. (1996) E-cadherin and its associated protein catenins, cancer invasion and metastasis. Br J Surg, 83, 437-446. Jolly, C. and Morimoto, R.I. (2000) Role of the heat shock response and molecular chaperones in oncogenesis and cell death. J Natl Cancer Inst, 92, 1564-1572. Kelley, W.L. and Georgopoulos, C. (1992) Chaperones and protein folding. Curr Opin Cell Biol, 4, 984-991. Khaitlina, S.Y. (2001) Functional specificity of actin isoforms. Int Rev Cytol, 202, 35-98. Kodera, Y., Isobe, K., Yamauchi, M., Kondoh, K., Kimura, N., Akiyama, S., Itoh, K., Nakashima, I. and Takagi, H. (1994) Expression of nm23 H-1 RNA levels in human gastric cancer tissues. A negative correlation with nodal metastasis. Cancer, 73, 259-265. Koyasu, S., Nishida, E., Kadowaki, T., Matsuzaki, F., Iida, K., Harada, F., Kasuga, M., Sakai, H. and Yahara, I. (1986) Two mammalian heat shock proteins, HSP90 and HSP100, are actin-binding proteins. Proc Natl Acad Sci U S A, 83, 8054-8058. Lambrechts, A., Van Troys, M. and Ampe, C. (2004) The actin cytoskeleton in normal and pathological cell motility. Int J Biochem Cell Biol, 36, 1890-1909. Landry, J. and Huot, J. (1995) Modulation of actin dynamics during stress and physiological stimulation by a signaling pathway involving p38 MAP kinase and heat-shock protein 27. Biochem Cell Biol, 73, 703-707. Landry, J. and Huot, J. (1999) Regulation of actin dynamics by stress-activated protein kinase 2 (SAPK2)-dependent phosphorylation of heat-shock protein of 27 kDa (Hsp27). Biochem Soc Symp, 64, 79-89. Laudanski, K. and Wyczechowska, D. (2006) The distinctive role of small heat shock proteins in oncogenesis. Arch Immunol Ther Exp (Warsz), 54, 103-111. Lavoie, J.N., Gingras-Breton, G., Tanguay, R.M. and Landry, J. (1993) Induction of Chinese hamster HSP27 gene expression in mouse cells confers resistance to heat shock. HSP27 stabilization of the microfilament organization. J Biol Chem, 268, 3420-3429. Leavitt, J., Ng, S.Y., Varma, M., Latter, G., Burbeck, S., Gunning, P. and Kedes, L. (1987) Expression of transfected mutant beta-actin genes: transitions toward the stable tumorigenic state. Mol Cell Biol, 7, 2467-2476. Li, C.Y., Lee, J.S., Ko, Y.G., Kim, J.I. and Seo, J.S. (2000) Heat shock protein 70 inhibits apoptosis downstream of cytochrome c release and upstream of caspase-3 activation. J Biol Chem, 275, 25665-25671. Lindquist, S. (1986) The heat-shock response. Annu Rev Biochem, 55, 1151-1191. Lindquist, S. and Craig, E.A. (1988) The heat-shock proteins. Annu Rev Genet, 22, 631-677. Macejak, D.G. and Luftig, R.B. (1991) Stabilization of actin filaments at early times after adenovirus infection and in heat-shocked cells. Virus Res, 19, 31-45. Malm, B., Larsson, H. and Lindberg, U. (1983) The profilin--actin complex: further characterization of profilin and studies on the stability of the complex. J Muscle Res Cell Motil, 4, 569-588. Matsumoto, Y., Tanaka, K., Harimaya, K., Nakatani, F., Matsuda, S. and Iwamoto, Y. (2001) Small GTP-binding protein, Rho, both increased and decreased cellular motility, activation of matrix metalloproteinase 2 and invasion of human osteosarcoma cells. Jpn J Cancer Res, 92, 429-438. Mehlen, P., Mehlen, A., Godet, J. and Arrigo, A.P. (1997) hsp27 as a switch between differentiation and apoptosis in murine embryonic stem cells. J Biol Chem, 272, 31657-31665. Meldrum, K.K., Burnett, A.L., Meng, X., Misseri, R., Shaw, M.B., Gearhart, J.P. and Meldrum, D.R. (2003) Liposomal delivery of heat shock protein 72 into renal tubular cells blocks nuclear factor-kappaB activation, tumor necrosis factor-alpha production, and subsequent ischemia-induced apoptosis. Circ Res, 92, 293-299. Meyer, T. and Hart, I.R. (1998) Mechanisms of tumour metastasis. Eur J Cancer, 34, 214-221. Mikolajczyk, M. and Nelson, M.A. (2004) Regulation of stability of cyclin-dependent kinase CDK11p110 and a caspase-processed form, CDK11p46, by Hsp90. Biochem J, 384, 461-467. Mitchison, T.J. and Cramer, L.P. (1996) Actin-based cell motility and cell locomotion. Cell, 84, 371-379. Mounier, N. and Arrigo, A.P. (2002) Actin cytoskeleton and small heat shock proteins: how do they interact? Cell Stress Chaperones, 7, 167-176. Neckers, L. and Ivy, S.P. (2003) Heat shock protein 90. Curr Opin Oncol, 15, 419-424. Nicholson-Dykstra, S., Higgs, H.N. and Harris, E.S. (2005) Actin dynamics: growth from dendritic branches. Curr Biol, 15, R346-357. Nicolson, G.L., Nawa, A., Toh, Y., Taniguchi, S., Nishimori, K. and Moustafa, A. (2003) Tumor metastasis-associated human MTA1 gene and its MTA1 protein product: role in epithelial cancer cell invasion, proliferation and nuclear regulation. Clin Exp Metastasis, 20, 19-24. Osada, M., Imaoka, S. and Funae, Y. (2004) Apigenin suppresses the expression of VEGF, an important factor for angiogenesis, in endothelial cells via degradation of HIF-1alpha protein. FEBS Lett, 575, 59-63. Peckham, M., Miller, G., Wells, C., Zicha, D. and Dunn, G.A. (2001) Specific changes to the mechanism of cell locomotion induced by overexpression of beta-actin. J Cell Sci, 114, 1367-1377. Piotrowicz, R.S., Hickey, E. and Levin, E.G. (1998) Heat shock protein 27 kDa expression and phosphorylation regulates endothelial cell migration. Faseb J, 12, 1481-1490. Piotrowicz, R.S. and Levin, E.G. (1997) Basolateral membrane-associated 27-kDa heat shock protein and microfilament polymerization. J Biol Chem, 272, 25920-25927. Poccia, F., Piselli, P., Di Cesare, S., Bach, S., Colizzi, V., Mattei, M., Bolognesi, A. and Stirpe, F. (1992) Recognition and killing of tumour cells expressing heat shock protein 65 kD with immunotoxins containing saporin. Br J Cancer, 66, 427-432. Poccia, F., Piselli, P., Vendetti, S., Bach, S., Amendola, A., Placido, R. and Colizzi, V. (1996) Heat-shock protein expression on the membrane of T cells undergoing apoptosis. Immunology, 88, 6-12. Ritossa, P. (1962) [Problems of prophylactic vaccinations of infants.]. Riv Ist Sieroter Ital, 37, 79-108. Robertson, S.P. (2005) Filamin A: phenotypic diversity. Curr Opin Genet Dev, 15, 301-307. Sadano, H., Taniguchi, S., Kakunaga, T. and Baba, T. (1988) cDNA cloning and sequence of a new type of actin in mouse B16 melanoma. J Biol Chem, 263, 15868-15871. Sahai, E. and Marshall, C.J. (2002) RHO-GTPases and cancer. Nat Rev Cancer, 2, 133-142. Samali, A., Holmberg, C.I., Sistonen, L. and Orrenius, S. (1999) Thermotolerance and cell death are distinct cellular responses to stress: dependence on heat shock proteins. FEBS Lett, 461, 306-310. Shiomi, T. and Okada, Y. (2003) MT1-MMP and MMP-7 in invasion and metastasis of human cancers. Cancer Metastasis Rev, 22, 145-152. Silacci, P., Mazzolai, L., Gauci, C., Stergiopulos, N., Yin, H.L. and Hayoz, D. (2004) Gelsolin superfamily proteins: key regulators of cellular functions. Cell Mol Life Sci, 61, 2614-2623. Small, J.V., Anderson, K. and Rottner, K. (1996) Actin and the coordination of protrusion, attachment and retraction in cell crawling. Biosci Rep, 16, 351-368. Sreedhar, A.S. and Csermely, P. (2004) Heat shock proteins in the regulation of apoptosis: new strategies in tumor therapy: a comprehensive review. Pharmacol Ther, 101, 227-257. Sreenath, T., Matrisian, L.M., Stetler-Stevenson, W., Gattoni-Celli, S. and Pozzatti, R.O. (1992) Expression of matrix metalloproteinase genes in transformed rat cell lines of high and low metastatic potential. Cancer Res, 52, 4942-4947. Steeg, P.S. (2003) Metastasis suppressors alter the signal transduction of cancer cells. Nat Rev Cancer, 3, 55-63. Sun, H.Q., Kwiatkowska, K. and Yin, H.L. (1995) Actin monomer binding proteins. Curr Opin Cell Biol, 7, 102-110. Takai, Y., Sasaki, T. and Matozaki, T. (2001) Small GTP-binding proteins. Physiol Rev, 81, 153-208. Tsai, M.F., Wang, C.C., Chang, G.C., Chen, C.Y., Chen, H.Y., Cheng, C.L., Yang, Y.P., Wu, C.Y., Shih, F.Y., Liu, C.C., Lin, H.P., Jou, Y.S., Lin, S.C., Lin, C.W., Chen, W.J., Chan, W.K., Chen, J.J. and Yang, P.C. (2006) A new tumor suppressor DnaJ-like heat shock protein, HLJ1, and survival of patients with non-small-cell lung carcinoma. J Natl Cancer Inst, 98, 825-838. Tsan, M.F. and Gao, B. (2004) Heat shock protein and innate immunity. Cell Mol Immunol, 1, 274-279. Udono, H., Yamano, T., Kawabata, Y., Ueda, M. and Yui, K. (2001) Generation of cytotoxic T lymphocytes by MHC class I ligands fused to heat shock cognate protein 70. Int Immunol, 13, 1233-1242. van Golen, K.L., Wu, Z.F., Qiao, X.T., Bao, L. and Merajver, S.D. (2000) RhoC GTPase overexpression modulates induction of angiogenic factors in breast cells. Neoplasia, 2, 418-425. Vandekerckhove, J. and Weber, K. (1978) At least six different actins are expressed in a higher mammal: an analysis based on the amino acid sequence of the amino-terminal tryptic peptide. J Mol Biol, 126, 783-802. Walsh, D., Grantham, J., Zhu, X.O., Wei Lin, J., van Oosterum, M., Taylor, R. and Edwards, M. (1999) The role of heat shock proteins in mammalian differentiation and development. Environ Med, 43, 79-87. Welch, M.D. (1999) The world according to Arp: regulation of actin nucleation by the Arp2/3 complex. Trends Cell Biol, 9, 423-427. Witke, W., Podtelejnikov, A.V., Di Nardo, A., Sutherland, J.D., Gurniak, C.B., Dotti, C. and Mann, M. (1998) In mouse brain profilin I and profilin II associate with regulators of the endocytic pathway and actin assembly. Embo J, 17, 967-976. Worthylake, R.A., Lemoine, S., Watson, J.M. and Burridge, K. (2001) RhoA is required for monocyte tail retraction during transendothelial migration. J Cell Biol, 154, 147-160. Yamane, M., Hattori, H., Sugito, K., Hayashi, Y., Tohnai, I., Ueda, M., Nishizawa, K. and Ohtsuka, K. (1995) Cotranslocation and colocalization of hsp40 (DnaJ) with hsp70 (DnaK) in mammalian cells. Cell Struct Funct, 20, 157-166. Yoshino, I., Goedegebuure, P.S., Peoples, G.E., Lee, K.Y. and Eberlein, T.J. (1994) Human tumor-infiltrating CD4+ T cells react to B cell lines expressing heat shock protein 70. J Immunol, 153, 4149-4158. Zhuge, Y. and Xu, J. (2001) Rac1 mediates type I collagen-dependent MMP-2 activation. role in cell invasion across collagen barrier. J Biol Chem, 276, 16248-16256.||摘要:||
Lung cancer has become the most common cause of cancer deaths in the world, and it gets worse each year. In previous studies, a novel tumor suppressor gene, HLJ-1, was found by utilizing microarray technology. In invasion/metastasis cell line model CL1-0, CL 1-1, CL 1-5, CL 1-5 F4 (invade ability and increase in order), HLJ-1 expression was associated with repressing lung cancer cell metastasis and invasion. HLJ1 (human liver DnaJ-like protein, also called DNAJB4), a member of Hsp 40 family, mainly participates in protein folding and assists cell against stress. When overexpressing HLJ1 protein, it reduces lung cancer cell abilities of proliferation, colony formation, invasion and migration. However, it is not yet clarified that how HLJ-1 suppresses lung cancer cell metastasis and invasion. Moreover, protein-protein interactions make further meaningful phenomena or situation in cell. Thus, we proposed HLJ-1 suppresses several lung cancer cell abilities through interacting with other proteins. We discovered HLJ1 interacts with heat shock protein 70 (HSC70), and beta-actin (ACTB) by immunoprecipitation and MALDI-TOF analysis in different cell lines. Furthermore, the complex of three components was also confirmed by co-immunoprecipitation and was found getting more in CL1-0 cell. ACTB is not only cell''s skeleton protein, but also control cell movement. By polymerizing ACTB or not, the cancer cell can stretch out lamellipodium and filopodium to make metastasis; when the cancer cell invades the basis membrane, reorganization of ACTB is necessary to modulate cell''s shape. So we wondered the complex of HLJ-1 and ACTB plays which role in lung cancer cell regarding metastasis and invasion. In immunofluorescent and immunoprecipitation experiments, we found HLJ1/HSC70/ACTB complex mainly in the cytoplasm, but little in the nucleus. In addition, we utilized mammal two hybrid assay and identified HLJ1/HSC70/ACTB complex in the cell. Meanwhile, it was also identified that HLJ-1 interacts with the C terminal of ACTB through J domain. When overexpressing J domain of HLJ1 to compete the interaction of ACTB, we found cancer cell invasion increases; when overexpressing C terminal of ACTB to compete interaction of HLJ1, we found cancer cell invasion also increases. Furthermore, with transfecting EYFP-ACTB plasmid, we analyzed ACTB polymerization affected by HLJ1 or not. We found ACTB polymerization increases in HLJ-1 silenced cell line. In this research, we found that HLJ1 forms a complex with HSC70, ACTB and mainly in cytoplasm. HLJ1 interacts with ACTB through J domain to influence ACTB polymerization, and suppress the cancer cell invasion ability. Follow-up we will further confirm how HLJ1 regulate ACTB polymerization, and make use of the research we can offer a regulate and control metastasis and invasion mechanism of cancer cell; perhaps this can apply on the treatment of cancer in future.
肺癌為國人癌症十大死因之一，且有逐年增加之趨勢。在本實驗室先前的研究中，利用肺腺癌CL1-0、CL 1-1、CL 1-5、CL 1-5F4 (侵入能力依序增加)作為模式細胞株，並利用cDNA微陣列(microarray)技術，篩選到一個具有抑制肺癌細胞轉移及侵入能力的新基因HLJ1 (human liver DnaJ-like protein,又稱DNAJB4)。HLJ1屬於熱休克蛋白40家族中的一員，主要參與蛋白質的折疊與抵抗外界壓力保護細胞。當大量表現HLJ1時，會大幅降低癌細胞的增生(proliferation)、聚落形成(colony formation)、侵入(in vitro invasion)和移動(in vitro migration)能力。HLJ1是透過何種機制來抑制癌細胞轉移、侵入能力，目前尚不清楚。然而，許多的蛋白是透過與其他蛋白交互作用來執行其功能。因此，本實驗藉由偵測與HLJ1結合之蛋白，來探討HLJ1所形成之複合物對肺腺癌細胞轉移及侵入有何影響。我們利用不同轉移能力的細胞株進行免疫沉澱並以質譜技術分析蛋白質可能身分，結果顯示HLJ1與HSC70、ACTB具有交互作用，且在CL1-0細胞株中有較高的表現量。以共免疫沉澱進行交叉實驗也確認HLJ1、HSC70與ACTB形成一複合物。ACTB不但為細胞骨架蛋白，也是細胞移動的重要蛋白。藉由ACTB的聚合重組，癌細胞可伸出絲狀偽足及片狀偽足增加癌細胞的轉移能力；當癌細胞進行變形運動侵入基底膜時，也須ACTB的重組使細胞形態改變。因此我們進一步探討HLJ1與ACTB結合在肺腺癌細胞轉移及侵入中扮演何種角色。以免疫螢光染色發現HLJ1/HSC70/ACTB複合物主要存在於細胞質，少部份會進入細胞核內。而分離核內/外蛋白並進行免疫沉澱，也證實此複合物確實在細胞質較多。另外，我們利用哺乳動物細胞蛋白交互作用也證明在細胞內HLJ1/HSC70/ACTB複合物確實存在，且HLJ1會透過J domain與ACTB的C端結合。進一步大量表現HLJ1的J domain來競爭HLJ1與ACTB的結合區域，發現癌細胞的侵入能力會增加；當大量表現ACTB的C端來競爭ACTB與HLJ1的結合區時，癌細胞的侵入能力也會增加。另外，我們轉染構築EYFP-ACTB的質體並以免疫沉澱法分析HLJ1對ACTB聚合的影響。由結果發現靜默HLJ1的細胞株，其ACTB的聚合會增加。總結而言，HLJ1會與HSC70、ACTB形成一複合物且主要位於細胞質。HLJ1可能透過J domain與ACTB結合，而影響ACTB的聚合，進而抑制肺腺癌細胞的侵入能力。後續我們將進一步探討HLJ1如何調控ACTB聚合的機制。藉由此研究我們可提供一個調控癌轉移及侵入的機制，或許在未來可應用於癌症的治療上。
|Appears in Collections:||分子生物學研究所|
Show full item record
TAIR Related Article
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.