SHP-1 has been proposed to be a tumor suppressor gene for several cancers. The expression of SHP-1 protein is diminished or abolished in most leukemia and lymphoma cell lines and tissues, and in some non-hematopoietic cancer cell lines, such as estrogen receptor (ER) negative breast cancer cell lines and some colorectal cancer cell lines. However, we do not know whether the reduced SHP-1 expression is the cause of cancer diseases or the secondary effect of cancer developments. Here, we first demonstrate that SHP-1 has general tumor suppressing function in SHP-1 transfected cell lines. Transfected SHP-1 inhibits the growth of three lymphoma/leukemia cell lines (Ramos, H9, Jurkat) and one breast cancer cell line (HTB26). We also demonstrate a possible molecular mechanism for the tumor suppressing function of SHP-1: SHP-1 inhibits cell growth partly by negative regulation of activated JAK kinase. In addition, we find, for the first time, that SHP-1 down-regulates the level of TYK2 kinase in H9 cells and of JAK1 kinase in HTB26 cells, by accelerating their degradation. The SHP-1 accelerated degradation of JAK1 kinase in HTB26 cells was blocked with the treatment of MG132, a specific inhibitor for proteasome-mediated proteolysis. Our data suggest a new function of SHP-1 in the regulation of proteasome-mediated degradation pathway.
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http://dx.doi.org/10.1002/jcb.10727 | DOI Listing |
Cancer Med
February 2025
Centre for Medical Research, Ningbo No.2 Hospital, Ningbo, China.
Background: Hepatocellular carcinoma (HCC) is one of the most common and highly lethal cancers worldwide. RIO kinase 1 (RIOK1), a protein kinase/ATPase that plays a key role in regulating translation and ribosome assembly, is associated with a variety of malignant tumors. However, the role of RIOK1 in HCC remains largely unknown.
View Article and Find Full Text PDFCancer Med
February 2025
Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.
Introduction: Immune checkpoint inhibitors (ICI) have improved the therapeutic arsenal in outpatient oncology care; however, data on necessity of hospitalizations associated with immune-related adverse events (irAEs) are scarce. Here, we characterized hospitalizations of patients undergoing ICI, from the prospective cohort study of the immune cooperative oncology group (ICOG) Hannover.
Methods: Between 12/2019 and 06/2022, 237 patients were included.
Biotechnol J
January 2025
Department of Biological Sciences, KAIST, Daejeon, Republic of Korea.
Increasing demand for adeno-associated virus (AAV) used in gene therapy highlights the need to enhance AAV production. When intracellular AAV2 and extracellular AAV9 were produced in HEK293T cells using the triple transfection method, apoptosis occurred during the AAV production. To mitigate apoptosis induced by AAV production, the pro-apoptotic BAX/BAK1 genes were knocked out in HEK293T cells.
View Article and Find Full Text PDFImmunol Cell Biol
January 2025
Steve and Cindy Rasmussen Institute for Genomic Medicine, Abigail Wexner Research Institute, Nationwide Children's Hospital, Columbus, OH, USA.
Natural killer (NK) cells are emerging agents for cancer therapy. Several different cytokines are used to generate NK cells for adoptive immunotherapy including interleukin (IL)-2, IL-12, IL-15 and IL-18 in solution, and membrane-bound IL-21. These cytokines drive NK cell activation through the integration of signal transducers and activators of transcription (STAT) and nuclear factor-kappa B (NF-κB) pathways, which overlap and synergize, making it challenging to predict optimal cytokine combinations for both proliferation and cytotoxicity.
View Article and Find Full Text PDFCancer
February 2025
Department of Palliative, Rehabilitation and Integrative Medicine, The University of Texas MD Anderson Cancer, Houston, Texas, USA.
Background: There is much concern that opioids administered as intravenous (iv) bolus for pain relief may inadvertently increase their risk for abuse. However, there is insufficient data to support this. The authors compared the abuse liability potential, analgesic efficacy, and adverse effect profile of fast (iv push) versus slow (iv piggyback) administration of iv hydromorphone among hospitalized patients requiring iv opioids for pain.
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