Abstract
BackgroundOral cancer malignancy consists of uncontrolled division of cells primarily in and around the floor of the oral cavity, gingiva, oropharynx, lower lip and base of the tongue. According to GLOBOCAN 2012 report, oral cancer is one of the most common cancers among males and females in India. Even though significant advancements have been made in the field of oral cancer treatment modalities, the overall prognosis for the patients has not improved in the past few decades and hence, this demands a new thrust for the identification of novel therapeutic targets in oral cancer. p21 Activated Kinases (PAKs) are potential therapeutic targets that are involved in numerous physiological functions. PAKs are serine-threonine kinases and they serve as important regulators of cytoskeletal dynamics and cell motility, transcription through MAP kinase cascades, death and survival signalling, and cell-cycle progression. Although PAKs are known to play crucial roles in cancer progression, the role and clinical significance of PAKs in oral cancer remains poorly understood.ResultsOur results suggest that PAK1 is over-expressed in oral cancer cell lines. Stimulation of Oral Squamous Cell Carcinoma (OSCC) cells with serum growth factors leads to PAK1 re-localization and might cause a profound cytoskeletal remodelling. PAK1 was also found to be involved in the invasion, migration and cytoskeletal remodelling of OSCC cells.ConclusionsOur study revealed that PAK1 may play a crucial role in the progression of OSCC. Studying the role of PAK1 and its substrates is likely to enhance our understanding of oral carcinogenesis and potential therapeutic value of PAKs in oral cancer.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2263-8) contains supplementary material, which is available to authorized users.
Highlights
Oral cancer malignancy consists of uncontrolled division of cells primarily in and around the floor of the oral cavity, gingiva, oropharynx, lower lip and base of the tongue
Our study suggests that p21 Activated Kinase 1 (PAK1) plays a crucial role in the progression of oral cancer and represents a potential therapeutic target in Oral Squamous Cell Carcinoma (OSCC)
Our study demonstrated that all the five OSCC cell lines differentially expressed PAK1 (Fig. 1a)
Summary
Oral cancer malignancy consists of uncontrolled division of cells primarily in and around the floor of the oral cavity, gingiva, oropharynx, lower lip and base of the tongue. PAKs are serine-threonine kinases and they serve as important regulators of cytoskeletal dynamics and cell motility, transcription through MAP kinase cascades, death and survival signalling, and cell-cycle progression. Carcinoma of lip and oral cavity is one of the most frequent causes of cancer deaths among males. Ninety percent of oral cancers are OSCC [2], PAKs were one of the first classes of Rho-GTPasesregulated kinases [3] to be identified. PAKs are considered prime regulators of the actin cytoskeleton and motility [5] Due to their central role in actin remodelling and their ability to activate Matrix metalloproteinases (MMPs), Rho GTPases play an important role in tumor cell invasion and metastasis [6]. PAKs have been implicated in a number of pathological conditions including cancer [24]
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