Nuclear Krüppel-like factor 4 expression is associated with human skin squamous cell carcinoma progression and metastasis

Abstract

Krüppel-like factor 4 (KLF4) is a transcription factor regulating cell growth and differentiation. It has been postulated as a tumor suppressor gene in several tumors including colon cancer and prostate cancer; whereas, it is activated in other tumors such as breast cancer and oropharyngeal carcinomas. To understand the significance KLF4 on clinicopathologic implications in human squamous cell carcinoma skin (SCC) progression, thirty six formalin-fixed paraffin-embedded samples of cutaneous SCC and 28 samples of Bowen's disease were stained with anti-KLF4 antibodies. A semiquantitative evaluation of the degree of staining intensity and localization of expression were analyzed and correlated with histological and clinical features. Nuclear KLF4 staining was seen in differentiated epithelium including suprabasal keratinocyte of non-lesional skin. Strong nuclear KLF4 staining was observed in tumor parts of both SCC and Bowen's disease, when compared with their non-tumor parts (p = 0.001). Increased expression of KLF4 protein and mRNA were found in squamous cell carcinoma cell line studies and fresh skin tissue respectively, using western blotting and semi-quantitative real time polymerase chain reaction (PCR). SCC with moderately and poorly differentiated tumors tend to have maturation independent (MI) staining pattern (p = 0.0004), compared to maturation dependent (MD) staining in well-differentiated tumors. Finally, constitutive nuclear KLF4 staining pattern was significantly associated with moderately and poorly differentiated tumors (p = 0.0006), and tumor metastasis (p = 0.024). We propose that KLF4 expression is associated with human skin SCC progression and metastases.

KLF4 is downregulated but not mutated during human esophageal squamous cell carcinogenesis and has tumor stage-specific functions

“…17,18 However, in other contexts, KLF4 exhibits behavior more consistent with an oncogene and is negatively associated with patient survival. [19][20][21] To explore the role of KLF4 in ESCC, we initially examined KLF4 expression in human ESCC using Oncomine. We identified 2 datasets 22,23 containing paired samples of ESCC and adjacent normal tissue; in both of these data sets, KLF4 expression was reduced in ESCC compared to adjacent normal (Fig.…”

Alterations in the Expression of p53, KLF4, and p21 in Neuroendocrine Lung Tumors

“…In this study, we describe several changes in KLF4 expression within a neoplastic spectrum, ranging from overexpression in preneoplastic benign lesions, such as tumorlets, to a significant lack of expression in typical and atypical carcinoids, to a high overexpression rate in neuroendocrine lung carcinomas. Similarly, KLF4 overexpression has been reported in oropharyngeal epidermoid carcinoma, 35 skin squamous cell carcinomas, 38 and intraductal breast carcinomas, 35 related to an aggressive course. 39 In conclusion, the expression of the proteins controlling relevant processes in the cell cycle is altered in neuroendocrine lung neoplasms, with the lack of KLF4 or p21 expression being associated with a statistically significant accumulation in cases with aggressive features in TC.…”

Elevated HOTAIR expression associated with cisplatin resistance in non-small cell lung cancer patients

“…Furthermore, we also observed that although there was a statistically significant difference, individual patients had the opposite result for Klf4 and HOTAIR expression. This result could be related to Klf4 function, which is different depending on subcellular localization (cell membrane, cytoplasm, or nucleus) (35,36). Thus, the specific functions and interactions of HOTAIR in the cell membrane, cytoplasm, and nucleus require further investigation.…”