Journal of Cell Science & Therapy
Open Access
ISSN: 2157-7013
+44 1300 500008
ISSN: 2157-7013
+44 1300 500008
P S Swarna Latha Beesetti, Mavuluri Jayadev and Rayala Suresh Kumar
Indian Institute of Technology Madras, India
Posters & Accepted Abstracts: J Cell Sci Ther
Non-melanoma skin cancer (NMSC) which includes both squamous cell carcinoma and basal cell carcinoma has become an increasing health problem over the recent years and is mainly caused by overexposure to Ultraviolet (UV) light. P21 activated kinase 1 (Pak1), a major mitogen responsive serine/threonine signaling kinase is a well known regulator of cytoskeletal remodeling that contributes to tumor formation. Alterations in Pak1 expression has been documented in many type of cancers. However, the contribution and direct role of Pak1 signaling to the etiology of Non-melanoma skin cancer has not yet been studied. In the current study, upon UV-B irradiation, we observed a significant increase in Pak1 activity and subsequently its nuclear localization in cell lines and mouse models. Further to understand the role of Pak1 in UV-B induced DNA damage response and survival, Pak1 overexpression and knockdown clones were generated in keratinocytes using viral transduction. Functional assays using these Pak1 modulated systems showed that Pak1 plays a significant role in cell survival upon UV-B exposure. Further, we elucidate the molecular mechanism of Pak1 activation by UV-B in keratinocyte cell lines is mediated by both the CPDs (Cyclo Pyrimidine Dimers) and EGFR pathway. In addition, we validated the above findings in a clinical setting by perceiving for Pak1 in various pre-malignant lesions of NMSC and observed that Pak1 expression is associated with histological evidence of chronic sun damage. We intend to focus on molecular mechanism and contribution of Pak1 to the transforming properties that promote the progression of skin lesions to more invasive tumors.
Email: swarnaiitm@gmail.com