Src/FAK-mediated Regulation of E-cadherin As a Mechanism for Controlling Collective Cell Movement: Insights from in Vivo Imaging

Overview

Journal Cell Adh Migr

Specialty Cell Biology

Date 2011 Aug 13

PMID 21836391

Citations 49

Authors

Alan Serrels

Marta Canel

Valerie G Brunton

Margaret C Frame

Affiliations

Soon will be listed here.

Abstract

Recent advances in confocal and multi-photon microscopy, together with fluorescent probe development, have enabled cancer biology studies to go beyond the culture dish and interrogate cancer-associated processes in the complex in vivo environment. Regulation of the tumor suppressor protein E-cadherin plays an important role in cancer development and progression and may contribute to the decision between 'single cell' and 'collective invasion' in vivo. Mounting evidence from in vitro and in vivo experiments places the two non-receptor protein tyrosine kinases Src and Focal Adhesion Kinase, at the heart of E-cadherin regulation, and the crosstalk between integrins and cadherins. Here we discuss recent insights, attained using high resolution fluorescent in vivo imaging, into the regulation of E-cadherin and collective invasion. We focus on the regulatory crosstalk between the Src/FAK signaling axis and E-cadherin in vivo.

Citing Articles

HS Donor SPRC Ameliorates Ischemic Stroke by Upregulating CD24.

Wang C, Li S, Li Q, Xi H, Li J, Zhu Q CNS Neurosci Ther. 2025; 31(2):e70243.

PMID: 39953809 PMC: 11829115. DOI: 10.1111/cns.70243.

Moscatilin Reverses EMT Progression and its Resulting Enhanced Invasion and Migration by Affecting the TGF-β Signaling Pathway in Bladder Cancer.

Li Z, Yang J, Chen L, Chen P, Liu C, Long X Anticancer Agents Med Chem. 2024; 24(14):1074-1084.

PMID: 38808719 DOI: 10.2174/0118715206307769240522075729.

Dasatinib suppresses collective cell migration through the coordination of focal adhesion and -cadherin in colon cancer cells.

Lu Y, Hou X, Koo H, Chao W Heliyon. 2024; 10(1):e23501.

PMID: 38187289 PMC: 10770570. DOI: 10.1016/j.heliyon.2023.e23501.

Focal adhesion kinase: from biological functions to therapeutic strategies.

Tan X, Yan Y, Song B, Zhu S, Mei Q, Wu K Exp Hematol Oncol. 2023; 12(1):83.

PMID: 37749625 PMC: 10519103. DOI: 10.1186/s40164-023-00446-7.

The Role of Cathepsin B in Pathophysiologies of Non-tumor and Tumor tissues: A Systematic Review.

Wang J, Zheng M, Yang X, Zhou X, Zhang S J Cancer. 2023; 14(12):2344-2358.

PMID: 37576397 PMC: 10414043. DOI: 10.7150/jca.86531.

References

Avizienyte E, Fincham V, Brunton V, Frame M . Src SH3/2 domain-mediated peripheral accumulation of Src and phospho-myosin is linked to deregulation of E-cadherin and the epithelial-mesenchymal transition. Mol Biol Cell. 2004; 15(6):2794-803. PMC: 420103. DOI: 10.1091/mbc.e03-12-0879. View

Friedl P, Wolf K . Tumour-cell invasion and migration: diversity and escape mechanisms. Nat Rev Cancer. 2003; 3(5):362-74. DOI: 10.1038/nrc1075. View

Macpherson I, Hooper S, Serrels A, McGarry L, Ozanne B, Harrington K . p120-catenin is required for the collective invasion of squamous cell carcinoma cells via a phosphorylation-independent mechanism. Oncogene. 2007; 26(36):5214-28. DOI: 10.1038/sj.onc.1210334. View

Avizienyte E, Wyke A, Jones R, McLean G, Westhoff M, Brunton V . Src-induced de-regulation of E-cadherin in colon cancer cells requires integrin signalling. Nat Cell Biol. 2002; 4(8):632-8. DOI: 10.1038/ncb829. View

Canel M, Serrels A, Miller D, Timpson P, Serrels B, Frame M . Quantitative in vivo imaging of the effects of inhibiting integrin signaling via Src and FAK on cancer cell movement: effects on E-cadherin dynamics. Cancer Res. 2010; 70(22):9413-22. PMC: 3079905. DOI: 10.1158/0008-5472.CAN-10-1454. View

Aligayer H, Boyd D, Heiss M, Abdalla E, Curley S, Gallick G . Activation of Src kinase in primary colorectal carcinoma: an indicator of poor clinical prognosis. Cancer. 2002; 94(2):344-51. DOI: 10.1002/cncr.10221. View

Brown E, Munn L, Fukumura D, Jain R . In vivo imaging of tumors. Cold Spring Harb Protoc. 2010; 2010(7):pdb.prot5452. PMC: 3891051. DOI: 10.1101/pdb.prot5452. View

Canel M, Serrels A, Anderson K, Frame M, Brunton V . Use of photoactivation and photobleaching to monitor the dynamic regulation of E-cadherin at the plasma membrane. Cell Adh Migr. 2010; 4(4):491-501. PMC: 3011267. DOI: 10.4161/cam.4.4.12661. View

Cartwright C, Kamps M, Meisler A, Pipas J, Eckhart W . pp60c-src activation in human colon carcinoma. J Clin Invest. 1989; 83(6):2025-33. PMC: 303927. DOI: 10.1172/JCI114113. View

10.

Bolen J, Veillette A, Schwartz A, Deseau V, Rosen N . Activation of pp60c-src protein kinase activity in human colon carcinoma. Proc Natl Acad Sci U S A. 1987; 84(8):2251-5. PMC: 304627. DOI: 10.1073/pnas.84.8.2251. View

11.

Christiansen J, Rajasekaran A . Reassessing epithelial to mesenchymal transition as a prerequisite for carcinoma invasion and metastasis. Cancer Res. 2006; 66(17):8319-26. DOI: 10.1158/0008-5472.CAN-06-0410. View

12.

de Beco S, Gueudry C, Amblard F, Coscoy S . Endocytosis is required for E-cadherin redistribution at mature adherens junctions. Proc Natl Acad Sci U S A. 2009; 106(17):7010-5. PMC: 2678428. DOI: 10.1073/pnas.0811253106. View

13.

Playford M, Vadali K, Cai X, Burridge K, Schaller M . Focal adhesion kinase regulates cell-cell contact formation in epithelial cells via modulation of Rho. Exp Cell Res. 2008; 314(17):3187-97. PMC: 2613854. DOI: 10.1016/j.yexcr.2008.08.010. View

14.

Friedl P, Noble P, Walton P, Laird D, Chauvin P, Tabah R . Migration of coordinated cell clusters in mesenchymal and epithelial cancer explants in vitro. Cancer Res. 1995; 55(20):4557-60. View

15.

Kedrin D, Gligorijevic B, Wyckoff J, Verkhusha V, Condeelis J, Segall J . Intravital imaging of metastatic behavior through a mammary imaging window. Nat Methods. 2008; 5(12):1019-21. PMC: 2820719. DOI: 10.1038/nmeth.1269. View

16.

Owens L, Xu L, Craven R, Dent G, Weiner T, Kornberg L . Overexpression of the focal adhesion kinase (p125FAK) in invasive human tumors. Cancer Res. 1995; 55(13):2752-5. View

17.

Guarino M, Rubino B, Ballabio G . The role of epithelial-mesenchymal transition in cancer pathology. Pathology. 2007; 39(3):305-18. DOI: 10.1080/00313020701329914. View

18.

Friedl P, Gilmour D . Collective cell migration in morphogenesis, regeneration and cancer. Nat Rev Mol Cell Biol. 2009; 10(7):445-57. DOI: 10.1038/nrm2720. View

19.

Cicchini C, Laudadio I, Citarella F, Corazzari M, Steindler C, Conigliaro A . TGFbeta-induced EMT requires focal adhesion kinase (FAK) signaling. Exp Cell Res. 2007; 314(1):143-52. DOI: 10.1016/j.yexcr.2007.09.005. View

20.

Wyckoff J, Wang Y, Lin E, Li J, Goswami S, Stanley E . Direct visualization of macrophage-assisted tumor cell intravasation in mammary tumors. Cancer Res. 2007; 67(6):2649-56. DOI: 10.1158/0008-5472.CAN-06-1823. View