Research Article: Cytokeratin-14 contributes to collective invasion of salivary adenoid cystic carcinoma

Date Published: February 2, 2017

Publisher: Public Library of Science

Author(s): Xiao-lei Gao, Jia-shun Wu, Min-xin Cao, Shi-yu Gao, Xiao Cen, Ya-ping Jiang, Sha-sha Wang, Ya-jie Tang, Qian-ming Chen, Xin-hua Liang, Yaling Tang, Tao Cai.


Collective invasion of cells plays a fundamental role in tissue growth, wound healing, immune response and cancer metastasis. This paper aimed to investigate cytokeratin-14 (CK14) expression and analyze its association with collective invasion in the invasive front of salivary adenoid cystic carcinoma (SACC) to uncover the role of collective invasion in SACC. Here, in the clinical data of 121 patients with SACC, the positive expression of CK14 was observed in 35/121(28.93%) of the invasive front of SACC. CK14 expression in the invasive front, local regional recurrence and distant metastasis were independent and significant prognostic factors in SACC patients. Then, we found that in an ex vivo 3D culture assay, CK14 siRNA receded the collective invasion, and in 2D monolayer culture, CK14 overexpression induced a collective SACC cell migration. These data indicated that the presence of characterized CK14+ cells in the invasive front of SACC promoted collective cell invasion of SACC and may be a biomarker of SACC with a worse prognosis.

Partial Text

Salivary adenoid cystic carcinoma (SACC) represented approximately 10% of all salivary neoplasm. SACC is by insidious invasion into adjacent tissue and hematogenous spread to distant organs [1–2]. Local invasion and distant metastasis are the main reasons to lead to the low overall survival, however, the molecular mechanism of invasion and metastasis in SACC still need to be investigated.

Collective cell invasion has been shown to be an important mechanism for normal epithelial formation and cancer invasion [20]. In this study, we analyzed the expression and role of CK14 in the invasion front of SACC patients. The data signified that the positive expression of CK14 in the invasive front was significantly associated with local regional recurrence, distant metastasis and poor prognosis of SACC patients. Then, we observed the phenomenon of collective cell invasion in SACC cells in vitro, and found that in an ex vivo 3D culture assay CK14 siRNA receded the collective invasion and CK14 overexpression induced collective migration in 2D monolayer culture, suggesting that CK14 promoted the collective invasion of SACC.




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