Dual role of hematopoietic progenitor kinase 1 (HPK1) as a positive regulator of 1α,25-dihydroxyvitamin D-induced differentiation and cell cycle arrest of AML cells and as a mediator of vitamin D resistance

Chen-Deutsch, Xiangwen; Studzinski, George P.

doi:10.4161/cc.19765

Cited by 13 publications

(8 citation statements)

References 55 publications

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“…One such agent which is used is 1α25-dihydroxyviatmin D (1,25D). Many studies have found that low doses of CA (5–10 µM) are able to potentiate the pro-differentiation effects of 1,25D and help sensitize leukemia cells including human HL-60, U937, MOLM-13 and mouse WEHI-3B cells [40,41,71,72,73,74,75,76,77,78] to its anticancer effects (Table 11). Furthermore, CA inhibited cell viability and induced apoptosis and cell cycle arrest in these cells using a multitude of different strategies.…”

Section: Anticancer Effects Of Carnosic Acid (Ca): In Vitro Studiesmentioning

confidence: 99%

Anticancer Effects of Rosemary (Rosmarinus officinalis L.) Extract and Rosemary Extract Polyphenols

2016

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Cancer cells display enhanced growth rates and a resistance to apoptosis. The ability of cancer cells to evade homeostasis and proliferate uncontrollably while avoiding programmed cell death/apoptosis is acquired through mutations to key signaling molecules, which regulate pathways involved in cell proliferation and survival. Compounds of plant origin, including food components, have attracted scientific attention for use as agents for cancer prevention and treatment. The exploration into natural products offers great opportunity to evaluate new anticancer agents as well as understand novel and potentially relevant mechanisms of action. Rosemary extract has been reported to have antioxidant, anti-inflammatory, antidiabetic and anticancer properties. Rosemary extract contains many polyphenols with carnosic acid and rosmarinic acid found in highest concentrations. The present review summarizes the existing in vitro and in vivo studies focusing on the anticancer effects of rosemary extract and the rosemary extract polyphenols carnosic acid and rosmarinic acid, and their effects on key signaling molecules.

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Section: Anticancer Effects Of Carnosic Acid (Ca): In Vitro Studiesmentioning

confidence: 99%

Anticancer Effects of Rosemary (Rosmarinus officinalis L.) Extract and Rosemary Extract Polyphenols

2016

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“…Cell differentiation is regulated in a cell cycle-dependent manner. For instance, the differentiation of hematopoietic cells is accompanied with G0/G1 phase cell cycle arrest [18][19][20]. In this study, the cell cycle analysis revealed that CDST could markedly induce a G0/G1 phase arrest in HL-60 cells, along with a significant reduction in G2/M and S phases.…”

Section: Discussionmentioning

confidence: 53%

1-Chloromethyl-6,7-dimethoxy-3,4-dihydro-1H-isoquinoline-2-sulfonic acid amide, a derivative of tetrahydroisoquinoline, induces granulocytic differentiation of the human leukemic HL-60 cells via G0/G1 phase arrest

Ju¹,

Pae²,

Kim³

et al. 2013

Health

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Tetrahydroisoquinolines are known to have various biological effects, including antitumor activity. This study investigated the effect of 1chloromethyl-6, 7-dimethoxy-3, 4-dihydro-1H-isoquinoline-2-sulfonic acid amide (CDST), a newly synthesized anticancer agent, on cellular differentiation and proliferation in HL-60 cells. Differentiation and proliferation of HL-60 cells were determined through expression of CD11b and CD14 surface antigens using flow cytometry and nitroblue tetrazolium (NBT) assay, and through analysis of cell cycle using propidium iodide staining, western blot analysis and immunoprecipitation, respectively. CDST induced the differentiation of HL-60, as shown by increased expression of differentiation surface antigen CD11b (but no significant change in CD14 expression) and increased NBT-reducing functional activity. DNA flow cytometry analysis indicated that CDST markedly induced a G0/G1 phase arrest of HL-60 cells. Subsequently, we examined the expression of G0/G1 phase cell cycle-related proteins, including cyclin-dependent kinases (CDKs), cyclins and cyclin dependent kinase inhibitors (CKIs), during the differentiation of HL-60. The levels of CDK2, CDK6, cyclin E and cyclin A were decreased, whereas steady-state levels of CDK4 and cyclin D1 were unaffected. The expression of the p27 Kip1 was markedly increased by CDST, but not p21 WAF1/Cip1. Moreover, CDST markedly enhanced the binding of p27 Kip1 with CDK2 and CDK6, resulting in the reduced activity of both kinases. Taken together, these results demonstrate that CDST is capable of inducing cellular differentiation and growth inhibition through p27 Kip1 protein-related G0/G1 phase arrest in HL-60 cells.

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“…In addition to autoimmune diseases, HPK1 is involved in the pathogenesis of cancer. It has been found that the level of HPK1 is altered in acute myeloid leukemia (35,36), bladder urothelial carcinoma (37), extramammary Paget's disease (38) and colon carcinoma (39). However, unlike in autoimmune diseases, the expression of HPK1 is increased in these types of cancer.…”

Section: Interactions Between Hematopoietic Progenitor Kinase 1 and Imentioning

confidence: 99%

Interactions between hematopoietic progenitor kinase 1 and its adaptor proteins

Zhang

Ding

Zhang

2017

Molecular Medicine Reports

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Hematopoietic progenitor kinase 1 (HPK1), also known as mitogen‑activated protein kinase kinase kinase kinase 1 is a serine/threonine protein kinase. It is involved in various cellular events, including mitogen‑activated protein kinase signaling, nuclear factor‑κB signaling, cytokine signaling, cellular proliferation and apoptosis, T cell receptor/B cell receptor signaling and T/B/dendritic cell‑mediated immune responses. Therefore, HPK1 has variety of roles in immunity, and is associated with the pathogenesis of autoimmune diseases, cancer, and the inflammatory response. In these cellular and immune events, HPK1 interacts with several adaptor proteins, including caspase recruitment domain family, member 11, hematopoietic cell‑specific protein 1, HPK1‑interacting protein of 55 kDa, the growth factor receptor‑bound protein 2 family, linker for activated T‑cells, the SH2 domain‑containing leukocyte protein of 76 kDa family, the v‑crk avian sarcoma virus CT10 oncogene homolog family, B‑cell adaptor molecule of 32 kDa and non‑catalytic region of tyrosine kinase adaptor protein. These adaptor proteins can couple HPK1 with various effector molecules, leading to the transmission of upstream signals to downstream targets. They are crucial in regulating the relocation, phosphorylation, activation and functions of HPK1. HPK1 can also phosphorylate certain proteins, consequently modulating their functions. This review aims to describe the adaptor proteins, which interact with HPK1, particularly focusing on their modes of interaction with HPK1, and the effects that these interactions cause.

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Dual role of hematopoietic progenitor kinase 1 (HPK1) as a positive regulator of 1α,25-dihydroxyvitamin D-induced differentiation and cell cycle arrest of AML cells and as a mediator of vitamin D resistance

Cited by 13 publications

References 55 publications

Anticancer Effects of Rosemary (Rosmarinus officinalis L.) Extract and Rosemary Extract Polyphenols

Anticancer Effects of Rosemary (Rosmarinus officinalis L.) Extract and Rosemary Extract Polyphenols

1-Chloromethyl-6,7-dimethoxy-3,4-dihydro-1H-isoquinoline-2-sulfonic acid amide, a derivative of tetrahydroisoquinoline, induces granulocytic differentiation of the human leukemic HL-60 cells via G0/G1 phase arrest

Interactions between hematopoietic progenitor kinase 1 and its adaptor proteins

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