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Int. J. Mol. Sci. 2015, 16(6), 12035-12050; doi:10.3390/ijms160612035

Dysregulation of PAK1 Is Associated with DNA Damage and Is of Prognostic Importance in Primary Esophageal Small Cell Carcinoma

1
Cancer Research Centre, Shantou University Medical College, Shantou 515063, China
2
Department of Information, Affiliated Cancer Hospital of Shantou University Medical College, Shantou 515031, China
3
Department of Biotherapy, Affiliated Cancer Hospital of Shantou University Medical College, Shantou 515031, China
4
Department of General Surgery, the Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai 519000, China
5
Department of Pathology, Central Hospital of Kaifeng, Kaifeng 475000, China
6
Thoracic Surgery, Affiliated Cancer Hospital of Shantou University Medical College, Shantou 515031, China
7
Tumor Tissue Bank, Affiliated Cancer Hospital of Shantou University Medical College, Shantou 515031, China
*
Author to whom correspondence should be addressed.
Academic Editor: William Chi-shing Cho
Received: 15 April 2015 / Accepted: 12 May 2015 / Published: 27 May 2015
(This article belongs to the Collection Advances in Molecular Oncology)
View Full-Text   |   Download PDF [3202 KB, uploaded 27 May 2015]   |  

Abstract

Primary esophageal small cell carcinoma (PESCC) is a rare, but fatal subtype of esophageal carcinoma. No effective therapeutic regimen for it. P21-activated kinase 1 (PAK1) is known to function as an integrator and an indispensable node of major growth factor signaling and the molecular therapy targeting PAK1 has been clinical in pipeline. We thus set to examine the expression and clinical impact of PAK1 in PESCC. The expression of PAK1 was detected in a semi-quantitative manner by performing immunohistochemistry. PAK1 was overexpressed in 22 of 34 PESCC tumors, but in only 2 of 18 adjacent non-cancerous tissues. Overexpression of PAK1 was significantly associated with tumor location (p = 0.011), lymph node metastasis (p = 0.026) and patient survival (p = 0.032). We also investigated the association of PAK1 with DNA damage, a driven cause for malignancy progression. γH2AX, a DNA damage marker, was detectable in 18 of 24 (75.0%) cases, and PAK1 expression was associated with γH2AX (p = 0.027). Together, PAK1 is important in metastasis and progression of PESCC. The contribution of PAK1 to clinical outcomes may be involved in its regulating DNA damage pathway. Further studies are worth determining the potentials of PAK1 as prognostic indicator and therapeutic target for PESCC. View Full-Text
Keywords: primary esophageal small cell carcinoma; p21-activated kinase 1; DNA damage; γH2AX; metastasis; prognosis primary esophageal small cell carcinoma; p21-activated kinase 1; DNA damage; γH2AX; metastasis; prognosis
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Gan, J.; Zhang, Y.; Ke, X.; Tan, C.; Ren, H.; Dong, H.; Jiang, J.; Chen, S.; Zhuang, Y.; Zhang, H. Dysregulation of PAK1 Is Associated with DNA Damage and Is of Prognostic Importance in Primary Esophageal Small Cell Carcinoma. Int. J. Mol. Sci. 2015, 16, 12035-12050.

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