The Roles of Oncogenic Phosphatase/Kinase in Tumors

Protein tyrosine phosphatases (PTPs) is the signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation, which is widely expressed in most tissues and plays a regulatory role in various cell signaling events that are important for a diversity of cell functions, such as cell migration. Protein tyrosine kinases (PTKs) are also important regulators of intracellular signaling pathways mediating multiple cellular activities. The mutations or other genetic alternations of oncogenic phosphatases or kinases encoding gene result in dysregulation of cell signaling pathways and malignant transformation. For example, Src homology 2 domain-containing phosphatase 2 (SHP2), encoded by the PTPN11 gene, is a non-receptor protein tyrosine phosphatase which is the first reported oncogenic tyrosine phosphatase. Except for Cell-autonomous mechanisms, tumor microenvironment-derived mutations of PTPN11 induce tumorigenesis, which depends on SHP2 catalytic activity. Studies have found PTPN11 activating mutations in the bone marrow microenvironment promote childhood myeloproliferative neoplasm development and progression through detrimental effects on haematopoietic stem cells. RAS (KRAS, NRAS and HRAS) is the most frequently mutated gene family in cancers. Increasingly studies revealed that genetic alternations of RAS contribute to the abnormal of microenvironment of cancer. For this reason, as we discuss the effects of oncogenic phosphatases or kinases in tumors, we should summarize this issue in two aspects, which are cell-autonomous mechanism and microenvironmental mutations. With the widely application of techniques for studying function of specific proteins, such as Cre/LoxP transgenic mice, reveal of the roles of oncogenic proteins in tumors has provided novel perspectives to target these proteins for therapeutic benefits.

The objective of this Research Topic is to provide a comprehensive overview of the roles of oncogenic phosphatase or kinase, derived from tumor cells or tumor microenvironment cells, in solid tumors as well as in non-solid tumors such as leukaemia. We will also summarize the current research progress on oncogenic protein regulators, such as SHP099 for SHP2 inhibition. We aim to suggest novel ideas or hypotheses that provide better understand in how oncogenic proteins regulates tumor progression and drive the discovery of novel therapeutic target for anti-tumor treatment.

We welcome Original Research, Reviews, and Mini-Review articles focusing on, but not limited to, the following topics:
•The effect of cell-autonomous mutations of oncogenic phosphatase/kinase to leukaemia or other well-known solid tumors
•The effect of oncogenic phosphatase/kinase mutations in tumor microenvironment to leukaemia or other well-known solid tumors
•Oncogenic protein inhibitors, past experiences, clinical phase and future perspectives