Critical roles of PTPN family members regulated by non-coding RNAs in tumorigenesis and immunotherapy

Abstract

Since tyrosine phosphorylation is reversible and dynamic in vivo, the phosphorylation state of proteins is controlled by the opposing roles of protein tyrosine kinases (PTKs) and protein tyrosine phosphatase (PTPs), both of which perform critical roles in signal transduction. Of these, intracellular non-receptor PTPs (PTPNs), which belong to the largest class I cysteine PTP family, are essential for the regulation of a variety of biological processes, including but not limited to hematopoiesis, inflammatory response, immune system, and glucose homeostasis. Additionally, a substantial amount of PTPNs have been identified to hold crucial roles in tumorigenesis, progression, metastasis, and drug resistance, and inhibitors of PTPNs have promising applications due to striking efficacy in antitumor therapy. Hence, the aim of this review is to summarize the role played by PTPNs, including PTPN1/PTP1B, PTPN2/TC-PTP, PTPN3/PTP-H1, PTPN4/PTPMEG, PTPN6/SHP-1, PTPN9/PTPMEG2, PTPN11/SHP-2, PTPN12/PTP-PEST, PTPN13/PTPL1, PTPN14/PEZ, PTPN18/PTP-HSCF, PTPN22/LYP, and PTPN23/HD-PTP, in human cancer and immunotherapy and to comprehensively describe the molecular pathways in which they are implicated. Given the specific roles of PTPNs, identifying potential regulators of PTPNs is significant for understanding the mechanisms of antitumor therapy. Consequently, this work also provides a review on the role of non-coding RNAs (ncRNAs) in regulating PTPNs in tumorigenesis and progression, which may help us to find effective therapeutic agents for tumor therapy.

Pan-cancer analysis revealing that PTPN2 is a indicator of risk stratification for acute myeloid leukemia identification of high-risk patients

“…Intracellular non-receptor PTPs, the largest of the cysteine PTP family, are critical for the regulation of a variety of biological processes, including but not limited to hematopoietic, in ammatory response, immune system and glucose homeostasis, and play an important role in the occurrence, development, metastasis and drug resistance of tumors [13]. However, comprehensive analysis of PTPNs is still missing at the pan-cancer level, especially in AML, and most studies focus on proving the clinical value of PTPN1 expression and PTPN11 mutation in AML [14; 15].…”

PTPN2 in the Immunity and Tumor Immunotherapy: A Concise Review

“…PTPN2 exerts the above-mentioned function mainly via the JAK/STAT signaling pathway in either immune-cold or immune-hot tumors [ 67 ]. Although protein kinase B (AKT), Src family kinase (SFK), MEK/ERK pathways have also been reported to interact with PTPN2 signaling, JAK/STAT is still the major signaling pathway to enhance the efficacy of ICIs in tumors [ 3 , 68 , 69 ].…”

“…The human genome encodes 107 PTPs, which are divided into four families according to the amino acid sequence of the catalytic domain ( Table 1 ) [ 2 ]. PTPN2 belongs to the intracellular non-receptor PTP subgroup, the classical PTP subfamily, the largest class I cysteine PTP family [ 3 ].…”

Cell marathon: long-distance cell migration and metastasis-associated gene analysis using a folding paper system

“…PTPN11 has been indicated in JAK/STAT, JNK, and NF-κB signaling, which have strong associations with various human cancers. 41 PTPN2 can inactivate STAT3 signaling and prevent hepato-cytes from progressing to HCC. 42 PTPN9 can suppress HCC growth and metastasis by inhibiting the AKT pathway.…”