**7. References**


p130Cas and p140Cap as the Bad and Good Guys in

and tumor progression. *Nat Med* 15: 1163-9.

involved in cell spreading. *Mol Biol Cell* 15: 787-800.

endothelial growth factor signaling. *J Cell Biol* 157: 149-60.

protein-coupled receptors. *Sci STKE* 2000: RE1.

progression. *Exp Cell Res* 284: 99-110.

mice lacking p130Cas. *Nat Genet* 19: 361-5.

from in vivo studies. *Nat Rev Mol Cell Biol* 9: 690-701.

junctions and cancer pathogenesis. *Curr Opin Cell Biol* 21: 694-700.

*Proteome Res* 4: 306-15.

*EMBO J* 26: 2843-55.

1721-33.

*Biol* 5: 816-26.

281: 2430-40.

*Opin Cell Biol* 21: 177-84.

*Biol* 23: 333-40.

Breast Cancer Cell Progression to an Invasive Phenotype 419

DeGiorgis JA, Jaffe H, Moreira JE, Carlotti CG, Jr., Leite JP, Pant HC *et al* (2005).

Desgrosellier JS, Barnes LA, Shields DJ, Huang M, Lau SK, Prevost N *et al* (2009). An

Di Stefano P, Cabodi S, Boeri Erba E, Margaria V, Bergatto E, Giuffrida MG *et al* (2004).

Di Stefano P, Damiano L, Cabodi S, Aramu S, Tordella L, Praduroux A *et al* (2007). p140Cap

Dorssers LC, Van der Flier S, Brinkman A, van Agthoven T, Veldscholte J, Berns EM *et al*

Eliceiri BP, Puente XS, Hood JD, Stupack DG, Schlaepfer DD, Huang XZ *et al* (2002). Src-

Feigin ME, Muthuswamy SK (2009). Polarity proteins regulate mammalian cell-cell

Giancotti FG (2003). A structural view of integrin activation and signaling. *Dev Cell* 4: 149-51. Guo W, Giancotti FG (2004). Integrin signalling during tumour progression. *Nat Rev Mol Cell* 

Gutkind JS (2000). Regulation of mitogen-activated protein kinase signaling networks by G

Heasman SJ, Ridley AJ (2008). Mammalian Rho GTPases: new insights into their functions

Hodgson JG, Malek T, Bornstein S, Hariono S, Ginzinger DG, Muller WJ *et al* (2005). Copy

Holcomb M, Rufini A, Barila D, Klemke RL (2006). Deregulation of proteasome function

Honda H, Oda H, Nakamoto T, Honda Z, Sakai R, Suzuki T *et al* (1998). Cardiovascular

Hsia DA, Mitra SK, Hauck CR, Streblow DN, Nelson JA, Ilic D *et al* (2003). Differential regulation of cell motility and invasion by FAK. *J Cell Biol* 160: 753-67. Hynes NE, MacDonald G (2009). ErbB receptors and signaling pathways in cancer. *Curr* 

Hynes RO (2004). The emergence of integrins: a personal and historical perspective. *Matrix* 

tumorigenic receptor tyrosine kinase signaling. *Cancer Res* 65: 9695-704. Holbro T, Civenni G, Hynes NE (2003). The ErbB receptors and their role in cancer

number aberrations in mouse breast tumors reveal loci and genes important in

induces Abl-mediated cell death by uncoupling p130CAS and c-CrkII. *J Biol Chem*

anomaly, impaired actin bundling and resistance to Src-induced transformation in

Phosphoproteomic analysis of synaptosomes from human cerebral cortex. *J* 

integrin alpha(v)beta(3)-c-Src oncogenic unit promotes anchorage-independence

P130Cas-associated protein (p140Cap) as a new tyrosine-phosphorylated protein

protein suppresses tumour cell properties, regulating Csk and Src kinase activity.

(2001). Tamoxifen resistance in breast cancer: elucidating mechanisms. *Drugs* 61:

mediated coupling of focal adhesion kinase to integrin alpha(v)beta5 in vascular


Berx G, Raspe E, Christofori G, Thiery JP, Sleeman JP (2007). Pre-EMTing metastasis?

Berx G, Van Roy F (2001). The E-cadherin/catenin complex: an important gatekeeper in

Bouton AH, Riggins RB, Bruce-Staskal PJ (2001). Functions of the adapter protein Cas: signal convergence and the determination of cellular responses. *Oncogene* 20: 6448-58. Brabek J, Constancio SS, Shin NY, Pozzi A, Weaver AM, Hanks SK (2004). CAS promotes

Buettner R, Mesa T, Vultur A, Lee F, Jove R (2008). Inhibition of Src family kinases with

Burnham MR, Harte MT, Richardson A, Parsons JT, Bouton AH (1996). The identification of

Cabodi S, del Pilar Camacho-Leal M, Di Stefano P, Defilippi P (2010a) Integrin signalling adaptors: not only figurants in the cancer story. *Nat Rev Cancer* 10: 858-70. Cabodi S, Di Stefano P, Leal Mdel P, Tinnirello A, Bisaro B, Morello V *et al* (2010b) Integrins

Cabodi S, Morello V, Masi A, Cicchi R, Broggio C, Distefano P *et al* (2008). Convergence of

Cabodi S, Moro L, Baj G, Smeriglio M, Di Stefano P, Gippone S *et al* (2004). p130Cas interacts

Cabodi S, Tinnirello A, Bisaro B, Tornillo G, del Pilar Camacho-Leal M, Forni G *et al* (2010c)

Cabodi S, Tinnirello A, Di Stefano P, Bisaro B, Ambrosino E, Castellano I *et al* (2006).

Chin LS, Nugent RD, Raynor MC, Vavalle JP, Li L (2000). SNIP, a novel SNAP-25-interacting protein implicated in regulated exocytosis. *J Biol Chem* 275: 1191-200. Choi YH, Ahn JH, Kim SB, Jung KH, Gong GY, Kim MJ *et al* (2009). Tissue microarray-based

Collins MO, Yu L, Coba MP, Husi H, Campuzano I, Blackstock WP *et al* (2005). Proteomic analysis of in vivo phosphorylated synaptic proteins. *J Biol Chem* 280: 5972-82. Damiano L, Di Stefano P, Camacho Leal MP, Barba M, Mainiero F, Cabodi S *et al* (2010)

Damiano L, Le Devedec S, Di Stefano P, Repetto D, Lalai R, Truong L *et al* (2011). p140Cap

tumour cell scatter and proliferation. *Oncogene* 29: 3677-90.

impaired cortactin phosphorylation. *Oncogene*. In Press

invasiveness of Src-transformed cells. *Oncogene* 23: 7406-15.

and signal transduction. *Adv Exp Med Biol* 674: 43-54.

Egr-1 expression. *J Cell Physiol*.

breast cancer cells. *J Cell Sci* 117: 1603-11.

in cancer. *Nat Rev Cancer* 4: 118-32.

6: 1766-74.

2467-72.

3796-808.

1337-43.

Recapitulation of morphogenetic processes in cancer. *Clin Exp Metastasis* 24: 587-97.

breast cancer tumorigenesis and malignant progression. *Breast Cancer Res* 3: 289-93.

dasatinib blocks migration and invasion of human melanoma cells. *Mol Cancer Res*

p130cas-binding proteins and their role in cellular transformation. *Oncogene* 12:

integrins and EGF receptor signaling via PI3K/Akt/FoxO pathway in early gene

with estrogen receptor alpha and modulates non-genomic estrogen signaling in

p130Cas is an essential transducer element in ErbB2 transformation. *FASEB J* 24:

p130Cas as a new regulator of mammary epithelial cell proliferation, survival, and HER2-neu oncogene-dependent breast tumorigenesis. *Cancer Res* 66: 4672-80. Cavallaro U, Christofori G (2004). Cell adhesion and signalling by cadherins and Ig-CAMs

study of patients with lymph node-negative breast cancer shows that HER2/neu overexpression is an important predictive marker of poor prognosis. *Ann Oncol* 20:

p140Cap dual regulation of E-cadherin/EGFR cross-talk and Ras signalling in

suppresses the invasive properties of highly metastatic MTLn3-EGFR cells via


p130Cas and p140Cap as the Bad and Good Guys in

enters the stage. *Trends Cell Biol* 10: 111-9.

assembly and maturation. *J Cell Biol* 186: 571-87.

of other cell interactions. *Mol Biol Cell* 18: 2013-25.

phosphorylation-dependent manner. *Embo J* 13: 3748-56.

Streuli CH (2009). Integrins and cell-fate determination. *J Cell Sci* 122: 171-7.

growth control. *Cell Mol Life Sci* 67: 1025-48.

kinase signaling. *J Clin Invest* 119: 252-66.

*Cell Biol* 3: 785-92.

*Embo J* 23: 1739-48.

*Chem* 271: 31222-6.

*Cell* 127: 1015-26.

226: 214-22.

*Eur J Cell Biol*.

Breast Cancer Cell Progression to an Invasive Phenotype 421

Muller WJ, Ho J, Siegel PM (1998). Oncogenic activation of Neu/ErbB-2 in a transgenic

Muthuswamy SK, Li D, Lelievre S, Bissell MJ, Brugge JS (2001). ErbB2, but not ErbB1,

O'Neill GM, Fashena SJ, Golemis EA (2000). Integrin signalling: a new Cas(t) of characters

Oser M, Yamaguchi H, Mader CC, Bravo-Cordero JJ, Arias M, Chen X *et al* (2009). Cortactin

Peinado H, Olmeda D, Cano A (2007). Snail, Zeb and bHLH factors in tumour progression: an alliance against the epithelial phenotype? *Nat Rev Cancer* 7: 415-28. Perrais M, Chen X, Perez-Moreno M, Gumbiner BM (2007). E-cadherin homophilic ligation

Pylayeva Y, Gillen KM, Gerald W, Beggs HE, Reichardt LF, Giancotti FG (2009). Ras- and

Qian X, Karpova T, Sheppard AM, McNally J, Lowy DR (2004). E-cadherin-mediated

Reynolds AB, Carnahan RH (2004). Regulation of cadherin stability and turnover by p120ctn: implications in disease and cancer. *Semin Cell Dev Biol* 15: 657-63. Ridley AJ, Schwartz MA, Burridge K, Firtel RA, Ginsberg MH, Borisy G *et al* (2003). Cell migration: integrating signals from front to back. *Science* 302: 1704-9. Riggins RB, Quilliam LA, Bouton AH (2003). Synergistic promotion of c-Src activation and cell migration by Cas and AND-34/BCAR3. *J Biol Chem* 278: 28264-73. Sakai R, Iwamatsu A, Hirano N, Ogawa S, Tanaka T, Mano H *et al* (1994). A novel signaling

Salgia R, Avraham S, Pisick E, Li JL, Raja S, Greenfield EA *et al* (1996). The related adhesion

Sawada Y, Tamada M, Dubin-Thaler BJ, Cherniavskaya O, Sakai R, Tanaka S *et al* (2006).

Takahashi K, Suzuki K (1996). Density-dependent inhibition of growth involves prevention

Tikhmyanova N, Little JL, Golemis EA (2010) CAS proteins in normal and pathological cell

Tornillo G, Bisaro B, Camacho-Leal MD, Galie M, Provero P, Di Stefano P *et al* (2010)

reinitiates proliferation and induces luminal repopulation in epithelial acini. *Nat* 

regulates cofilin and N-WASp activities to control the stages of invadopodium

inhibits cell growth and epidermal growth factor receptor signaling independently

PI3K-dependent breast tumorigenesis in mice and humans requires focal adhesion

adhesion inhibits ligand-dependent activation of diverse receptor tyrosine kinases.

molecule, p130, forms stable complexes in vivo with v- Crk and v-Src in a tyrosine

focal tyrosine kinase forms a complex with paxillin in hematopoietic cells. *J Biol* 

Force sensing by mechanical extension of the Src family kinase substrate p130Cas.

of EGF receptor activation by E-cadherin-mediated cell-cell adhesion. *Exp Cell Res*

p130Cas promotes invasiveness of three-dimensional ErbB2-transformed mammary acinar structures by enhanced activation of mTOR/p70S6K and Rac1.

mouse model for breast cancer. *Biochem Soc Symp* 63: 149-57.


Ito H, Atsuzawa K, Sudo K, Di Stefano P, Iwamoto I, Morishita R *et al* (2008).

Janssen H, Marynen P (2006). Interaction partners for human ZNF384/CIZ/NMP4--zyxin as

Jaworski J, Kapitein LC, Gouveia SM, Dortland BR, Wulf PS, Grigoriev I *et al* (2009).

Kim W, Seok Kang Y, Soo Kim J, Shin NY, Hanks SK, Song WK (2008). The integrin-coupled

Kioka N, Ueda K, Amachi T (2002). Vinexin, CAP/ponsin, ArgBP2: a novel adaptor protein

Kiyokawa E, Hashimoto Y, Kobayashi S, Sugimura H, Kurata T, Matsuda M (1998). Activation of Rac1 by a Crk SH3-binding protein, DOCK180. *Genes Dev* 12: 3331-6. Klemke RL, Leng J, Molander R, Brooks PC, Vuori K, Cheresh DA (1998). CAS/Crk

Kobashigawa Y, Sakai M, Naito M, Yokochi M, Kumeta H, Makino Y *et al* (2007). Structural

Kostic A, Sheetz MP (2006). Fibronectin rigidity response through Fyn and p130Cas

Kurebayashi J (2001). Biological and clinical significance of HER2 overexpression in breast

Latour S, Veillette A (2001). Proximal protein tyrosine kinases in immunoreceptor signaling.

Matsuyama M, Mizusaki H, Shimono A, Mukai T, Okumura K, Abe K *et al* (2005). A novel

Montagna C, Andrechek ER, Padilla-Nash H, Muller WJ, Ried T (2002). Centrosome

Morello V, Cabodi S, Sigismund S, Camacho-Leal MP, Repetto D, Volante M *et al* (2011)

Moro L, Venturino M, Bozzo C, Silengo L, Altruda F, Beguinot L *et al* (1998). Integrins

Mukohara T (2004) Mechanisms of resistance to anti-human epidermal growth factor

activation of MAPK cascade in mouse fetal gonad. *Genes Cells* 10: 421-34. Mitra SK, Hanson DA, Schlaepfer DD (2005). Focal adhesion kinase: in command and

isoform of Vinexin, Vinexin gamma, regulates Sox9 gene expression through

abnormalities, recurring deletions of chromosome 4, and genomic amplification of HER2/neu define mouse mammary gland adenocarcinomas induced by mutant

beta1 integrin controls EGFR signaling and tumorigenic properties of lung cancer

induce activation of EGF receptor: role in MAP kinase induction and adhesion-

a mediator for p130CAS signaling? *Exp Cell Res* 312: 1194-204.

synaptic complex. *J Neurochem* 107: 61-72.

factor-beta signaling. *Mol Biol Cell* 19: 2135-46.

protein CRK. *Nat Struct Mol Biol* 14: 503-10.

cancer. *Breast Cancer* 8: 45-51.

*Curr Opin Immunol* 13: 299-306. Massague J (2008). TGFbeta in Cancer. *Cell* 134: 215-30.

HER2/neu. *Oncogene* 21: 890-8.

dependent cell survival. *Embo J* 17: 6622-32.

receptor 2 agents in breast cancer. *Cancer Sci* 102: 1-8.

cells. *Oncogene*.

recruitment to the leading edge. *Mol Biol Cell* 17: 2684-95.

control of cell motility. *Nat Rev Mol Cell Biol* 6: 56-68.

plasticity. *Neuron* 61: 85-100.

*Funct* 27: 1-7.

140: 961-72.

Characterization of a multidomain adaptor protein, p140Cap, as part of a pre-

Dynamic microtubules regulate dendritic spine morphology and synaptic

signaling adaptor p130Cas suppresses Smad3 function in transforming growth

family regulating cytoskeletal organization and signal transduction. *Cell Struct* 

coupling serves as a "molecular switch" for induction of cell migration. *J Cell Biol*

basis for the transforming activity of human cancer-related signaling adaptor


**20** 

 *Taiwan* 

Shao-Wen Hung, Chiao-Li Chu, Yu-Ching Chang and Shu-Mei Liang

**Fibrillar Human Serum Albumin Suppresses** 

Breast cancer is one of the most common cancers among women worldwide and approximately one-third of women diagnosed will eventually develop metastases and die (Jemal et al, 2010). Breast cancer is heterogeneous at the molecular, histopathologic and clinical levels and is commonly classified into several categories according to multiple schemes, each based on different criteria. A typical description of breast cancer can be comprised of tumor grade, histologic type, tumor stage, and the expression of proteins and genes etc. (McSherry et al, 2007). Normal non-cancerous cells are differentiated and have specific cell shapes and functions; whereas, cancer cells lose differentiation (dedifferentiate), have less uniform nuclei, and exhibit uncontrolled cell division. Pathologists, therefore, determine breast cancer by grade according to the degree of differentiation of cells compared to normal breast cells: highly differentiated (low grade), moderately differentiated (intermediate grade), and poorly differentiated (high grade). Cancers classified as high grade generally have a worse prognosis (McSherry et al, 2007). The majority of breast cancers are derived from the epithelium lining the ducts or lobules of the breast. They can be classified histologically according to characteristics seen upon light microscopy of biopsy specimens. Histologic classification is divided into: ductal carcinoma in situ (DCIS), invasive ductal carcinoma, and invasive lobular carcinoma (McSherry et al, 2007). Breast cancer can further be classified using the TMN Classification of Malignant Tumors, TMN stage is based on tumor size, lymph node micrometastasis, and macrometastasis, where 'T' describes tumor size; 'N' indicates whether or not the tumor has spread to the lymph nodes; and 'M' indicates whether or not distant metastasis has occurred. Larger tumor size with lymph nodal spread and distal metastasis has a worse prognosis (Gonzalez-Angulo et al, 2007). Expression of certain proteins and genes can also be used to classify breast cancer (McGrogan et al, 2008; Stickeler et al, 2009). Whole-genome analysis using expression microarray and immunohistochemical analysis has revolutionized the understanding of breast carcinomas in recent years, and led to the discovery of five distinct subtypes of breast carcinomas (luminal A, luminal B, HER-2 overexpression, basallike, and normal-like), each with unique recognizable phenotypes and clinical outcomes (McGrogan et al, 2008; Stickeler et al, 2009). By using classification to characterize each cancer patient, it may help select the suitable treatment strategies to achieve an optimal

**1. Introduction** 

**1.1 Breast cancer classification** 

outcome and increase therapeutic efficacy.

**Breast Cancer Cell Growth and Metastasis** 

*Agricultural Biotechnology Research Center, Academia Sinica, Taipei* 

