part of 10.2217/fon-2015-0057 © 2016 Future Medicine Ltd REVIEW Implication of protein tyrosine phosphatase SHP-1 in cancer-related signaling pathways Yadhu Sharma 1 , Altaf Ahmad 2 , Samina Bashir 1 , Asif Elahi 3 & Farah Khan* ,1 1 Department of Biochemistry, Faculty of Science, Jamia Hamdard, New Delhi-110062, India 2 Department of Botany, Aligarh Muslim University, Aligarh, Uttar Pradesh-202002, India 3 Centre for Cellular & Molecular Biology (Council for Scientific & Industrial Research), Uppal Road, Hyderabad, Telangana-500007, India *Author for correspondence: farahkhan3@gmail.com The altered expression of SHP-1 (SH2 domain-containing protein tyrosine phosphatase) as a consequence of promoter hypermethylation or mutations has evidently been linked to cancer development. The notion of being a cancer drug target is conceivable as SHP-1 negatively regulates cell cycle and infammatory pathways which are an inevitable part of oncogenic transformation. In the present review, we try to critically analyze the role of SHP-1 in cancer progression via regulating the above mentioned pathways with the major emphasis on cell cycle components and JAK/STAT pathway, commencing with the SHP-1 biology in immune cell signaling. Lastly, we have provided the future directions for researchers to encourage SHP-1 as a prognostic marker and curative target for this debilitating disease called as cancer. First draft submitted: 10 December 2015; Accepted for publication: 14 January 2016; Published online: 18 March 2016 KEYWORDS • cancer • cyclin dependent kinases • motheaten mice • SHP-1 • viable motheaten mice • p27 kip1 • STAT3 In the past decades, considerable research on protein tyrosine phosphatases (PTPs) structure and function marks their importance as potential therapeutic targets in many debilitating diseases including cancer. So far, more than 100 phosphatases have been reported to be encoded by human genome belonging to the PTP family. SHP-1 is a nonreceptor tyrosine phosphatase comprising a catalytic PTPase domain flanked by various N and C terminal residues engaged in secondary and tertiary structure formation like in the SH2 domain [1] So far, more than 1000 peer-reviewed litera- ture has been published related to the structure and function of SH2 domain containing tyrosine phosphatase SHP-1. Although few researchers have exquisitely summarized the SHP-1 biology in a comprehensive review, the ongoing research unveils the newer function of this protein in various other tissues (other than hematopoietic origin) and in their associated malignancies. In the current review, we detailed the recent knowledge of SHP-1 immunobiology and its intricate signaling in the pathogenesis of cancer. SHP-1 protein structure The SHP-1 encoding gene, PTPN6, mapped to be located on chromosome 12 and 6 in human and mouse respectively [1] . The two promoters govern the expression of SHP-1 producing two types of transcripts namely (I) SHP-1 and (II) SHP-1, which slightly differ in the amino acid sequence but have almost similar enzymatic activity [2] . SHP-1 (also known as SHPTP-1, SHP, HCP and PTPIC) is a class I classical nonreceptor SH2 domain-containing protein tyrosine phosphatase predominantly expressed in hematopoietic cell and epithelial cells while exhibit low Future Oncol. (Epub ahead of print) ISSN 1479-6694 For reprint orders, please contact: reprints@futuremedicine.com