ERK phosphorylation functions in invadopodia formation in tongue cancer cells in a novel silicate fibre-based 3D cell culture system

Abstract

Extracellular signal-regulated kinases (ERKs) are enzymes that are involved in a variety of cell functions, and one in vitro study suggests that ERKs play a role in tongue cancer development by increasing cancer cell proliferation and migration. Using a novel 3-D cell culture system called Cellbed to mimic cancer cell morphology, a team headed by Ken-ichi Mukaisho at Shiga University of Medical Science, Japan found that ERKs activate cortactin (a protein located in the cell cytoplasm) and contribute to the formation of invadopodia (invasive cell protrusions associated with cancer cells) in tongue cancer cells and tumor development. The authors conclude that experimental 3-D cell culture systems employing Cellbed are easily implemented and useful for in vitro studies before conducting animal experiments and that they can be widely applied in cancer research.

References

[1] GLOBOCAN. Estimated cancer incidence, mortality and prevalence worldwide in 2012. http://globocan.iarc.fr/Pages/fact_sheets_population.aspx, 2012.

[2] Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. Torre LA1. CA Cancer J. Clin., 2015, 65: 87-108.

[3] Japan Society for Head and Neck Cancer. Registry committee. Report of Head and Neck Cancer Registry of Japan clinical statistics of registered patients, 2003. Jpn. J. Head Neck Cancer, 1–96 (2007).

[4] Saito S, . Mechanisms underlying cancer progression caused by ezrin overexpression in tongue squamous cell carcinoma. PLOS ONE, 2013, 8: e54881.

[5] Branco da Cunha C, . CD44 alternative splicing in gastric cancer cells is regulated by culture dimensionality and matrix stiffness. Biomaterials, 2016, 98: 152-162.

[6] Wirtz D, Konstantopoulos K, Searson PC. The physics of cancer: the role of physical interactions and mechanical forces in metastasis. Nat. Rev. Cancer, 2011, 11: 512-522.

[7] Friedl P, Sahai E, Weiss S, Yamada KM. New dimensions in cell migration. Nat. Rev. Mol. Cell Biol., 2012, 13: 743-747.

[8] Jaalouk DE, Lammerding J. Mechanotransduction gone awry. Nat. Rev. Mol. Cell Biol., 2009, 10: 63-73.

[9] Baker BM, Chen CS. Deconstructing the third dimension: how 3D culture microenvironments alter cellular cues. J. Cell. Sci., 2012, 125: 3015-3024.

[10] von der Mark K, Gauss V, von der Mark H, Müller P. Relationship between cell shape and type of collagen synthesised as chondrocytes lose their cartilage phenotype in culture. Nature, 1977, 267: 531-532.

[11] Petersen OW, Rønnov-Jessen L, Howlett AR, Bissell MJ. Interaction with basement membrane serves to rapidly distinguish growth and differentiation pattern of normal and malignant human breast epithelial cells. Proc. Natl. Acad. Sci. U. S. A., 1992, 89: 9064-9068.

[12] Yamaguchi Y, . Silicate fiber-based 3D cell culture system for anticancer drug screening. Anticancer Res., 2013, 33: 5301-5309.

[13] Ken-ichi M, . Morphology of various cancer cells using the silicate fiber scaffold Cellbed in a novel three-dimensional cell culture system. Gastroenterology, 2017, 152: S352-SS353.

[14] Tarone G, Cirillo D, Giancotti FG, Comoglio PM, Marchisio PC. Rous sarcoma virus-transformed fibroblasts adhere primarily at discrete protrusions of the ventral membrane called podosomes. Exp. Cell Res., 1985, 159: 141-157.

[15] Chen WT. Proteolytic activity of specialized surface protrusions formed at rosette contact sites of transformed cells. J. Exp. Zool., 1989, 251: 167-185.

[16] Alblazi KM, Siar CH. Cellular protrusions--lamellipodia, filopodia, invadopodia and podosomes--and their roles in progression of orofacial tumours: current understanding. Asian Pac. J. Cancer Prev., 2015, 16: 2187-2191.

[17] Wang S, . Study on invadopodia formation for lung carcinoma invasion with a microfluidic 3D culture device. PLoS One, 2013, 8: e56448.

[18] Tokui N, . Extravasation during bladder cancer metastasis requires cortactin‑mediated invadopodia formation. Mol. Med. Rep., 2014, 9: 1142-1146.

[19] Eckert MA, . Twist1-induced invadopodia formation promotes tumor metastasis. Cancer Cell., 2011, 19: 372-386.

[20] Caporale A, . Has desmoplastic response extent protective action against tumor aggressiveness in gastric carcinoma?. J. Exp. Clin. Cancer Res., 2001, 20: 21-24.

[21] Holliday DL, Brouilette KT, Markert A, Gordon LA, Jones JL. Novel multicellular organotypic models of normal and malignant breast: tools for dissecting the role of the microenvironment in breast cancer progression. Breast Cancer Res., 2009, 11

[22] Gurski LA, Jha AK, Zhang C, Jia X, Farach-Carson MC. Hyaluronic acid-based hydrogels as 3D matrices for in vitro evaluation of chemotherapeutic drugs using poorly adherent prostate cancer cells. Biomaterials, 2009, 30: 6076-6085.

[23] Fischbach C, . Engineering tumors with 3D scaffolds. Nat. Methods, 2007, 4: 855-860.

[24] Simon KA, . Metabolic response of lung cancer cells to radiation in a paper-based 3D cell culture system. Biomaterials, 2016, 95: 47-59.

[25] Pampaloni F, Reynaud EG, Stelzer EH. The third dimension bridges the gap between cell culture and live tissue. Nat. Rev. Mol. Cell Biol., 2007, 8: 839-845.

[26] Horning JL, . 3-D tumor model for in vitro evaluation of anticancer drugs. Mol. Pharm., 2008, 5: 849-862.

[27] Roberts PJ, Der CJ. Targeting the Raf-MEK-ERK mitogen-activated protein kinase cascade for the treatment of cancer. Oncogene, 2007, 26: 3291-3310.

[28] Theocharis S, . Extracellular signal-regulated kinase (ERK) expression and activation in mobile tongue squamous cell carcinoma: associations with clinicopathological parameters and patients survival. Tumour Biol., 2014, 35: 6455-6465.

[29] Degen M, Natarajan E, Barron P, Widlund HR, Rheinwald JG. MAPK/ERK-dependent translation factor hyperactivation and dysregulated laminin γ2 expression in oral dysplasia and squamous cell carcinoma. Am. J. Pathol., 2012, 180: 2462-2478.

[30] Ito A, . The subcellular localization and activity of cortactin is regulated by acetylation and interaction with Keap1. Sci. Signal., 2015, 8: ra120.

[31] Ni QF, . Cortactin promotes colon cancer progression by regulating ERK pathway. Int. J. Oncol., 2015, 47: 1034-1042.

[32] Lohcharoenkal W, . Role of H-Ras/ERK signaling in carbon nanotube-induced neoplastic-like transformation of human mesothelial cells. Front. Physiol., 2014, 5: 222.

[33] Kelley LC, Hayes KE, Ammer AG, Martin KH, Weed SA. Revisiting the ERK/Src cortactin switch. Commun. Integr. Biol., 2011, 4: 205-207.

[34] Martinez-Quiles N, Ho HY, Kirschner MW, Ramesh N, Geha RS. Erk/Src phosphorylation of cortactin acts as a switch on-switch off mechanism that controls its ability to activate N-WASP. Mol. Cell. Biol., 2004, 24: 5269-5280.