SCP4-STK35/PDIK1L complex is a dual phospho-catalytic signaling dependency in acute myeloid leukemia

Polyanskaya, Sofya A.; Moreno, Rosamaria Y.; Lü, Bin; Feng, Ruopeng; Yao, Yu; Irani, Seema; Klingbeil, Olaf; Yang, Zhaolin; Wei, Yiliang; Demerdash, Osama E.; Benjamin, Lukas A.; Weiss, Mitchell J.; Zhang, Yan Jessie; Vakoc, Christopher R.

doi:10.1016/j.celrep.2021.110233

“…Recent developments have emerged regarding the association between CTDSPL2 and tumors (14,15). However, the precise role of CTDSPL2 in NSCLC has not been clari ed.…”

Section: Discussionmentioning

confidence: 99%

“…CTDSPL2-mediated dephosphorylation of Snail inhibits its degradation, consequently enhancing TGFβ-induced EMT (13). In AML, CTDSPL2 dephosphorylates the kinases STK35 and PDIK1L, facilitating their interaction, in uencing the expression of genes related to amino acid biosynthesis and transport, and promoting the proliferation of AML cells (15). However, whether CTDSPL2 promotes NSCLC progression through the dephosphorylation of speci c substrates remains unclear.…”

Section: Discussionmentioning

confidence: 99%

“…In pancreatic cancer cells, CTDSPL2 knockdown upregulates p21 and p27 expression, resulting in the suppression of cell proliferation, migration and invasion by inducing mitotic defects (14). In acute myeloid leukemia (AML), CTDSPL2 dephosphorylates the kinases STK35 and PDIK1L, supporting the proliferation of AML cancer cells and affecting the expression of genes involved in amino acid biosynthesis and transport (15). However, until now, the biological functions and molecular mechanisms underlying the role of CTDSPL2 in NSCLC progression are completely unde ned.…”

Section: Introductionmentioning

confidence: 99%

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CTDSPL2 promotes the progression of non-small lung cancer through PI3K/AKT signaling via JAK1

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Carboxy-terminal domain small phosphatase like 2 (CTDSPL2), one of the haloacid dehalogenase phosphatases, is associated with several diseases including cancer. However, the role of CTDSPL2 and its regulatory mechanism in lung cancer remain unclear. Here, we aimed to explore the clinical implications, biological functions, and molecular mechanisms of CTDSPL2 in non-small cell lung cancer (NSCLC). CTDSPL2 was identified as a novel target of the tumor suppressor miR-193a-3p. CTDSPL2 expression was significantly elevated in NSCLC tissues. Database analysis showed that CTDSPL2 expression was negatively correlated with patient survival. Depletion of CTDSPL2 inhibited the proliferation, migration, and invasion of NSCLC cells, as well as tumor growth and metastasis in mouse models. Additionally, silencing of CTDSPL2 enhanced CD4+ T cell infiltration into tumors. Moreover, CTDSPL2 interacted with JAK1 and positively regulated JAK1 expression. Subsequent experiments indicated that CTDSPL2 activated the PI3K/AKT signaling pathway through the upregulation of JAK1, thereby promoting the progression of NSCLC. In conclusion, CTDSPL2 may play an oncogenic role in NSCLC progression by activating PI3K/AKT signaling via JAK1. These findings may provide a potential target for the diagnosis and treatment of NSCLC.

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CTDSPL2 promotes the progression of non-small lung cancer through PI3K/AKT signaling via JAK1

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Chen,

Yu

et al. 2024

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Carboxy-terminal domain small phosphatase like 2 (CTDSPL2), one of the haloacid dehalogenase phosphatases, is associated with several diseases including cancer. However, the role of CTDSPL2 and its regulatory mechanism in lung cancer remain unclear. Here, we aimed to explore the clinical implications, biological functions, and molecular mechanisms of CTDSPL2 in non-small cell lung cancer (NSCLC). CTDSPL2 was identified as a novel target of the tumor suppressor miR-193a-3p. CTDSPL2 expression was significantly elevated in NSCLC tissues. Database analysis showed that CTDSPL2 expression was negatively correlated with patient survival. Depletion of CTDSPL2 inhibited the proliferation, migration, and invasion of NSCLC cells, as well as tumor growth and metastasis in mouse models. Additionally, silencing of CTDSPL2 enhanced CD4+ T cell infiltration into tumors. Moreover, CTDSPL2 interacted with JAK1 and positively regulated JAK1 expression. Subsequent experiments indicated that CTDSPL2 activated the PI3K/AKT signaling pathway through the upregulation of JAK1, thereby promoting the progression of NSCLC. In conclusion, CTDSPL2 may play an oncogenic role in NSCLC progression by activating PI3K/AKT signaling via JAK1. These findings may provide a potential target for the diagnosis and treatment of NSCLC.

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Application and research progress of single cell sequencing technology in leukemia

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Leukemia is a malignant tumor with high heterogeneity and a complex evolutionary process. It is difficult to resolve the heterogeneity and clonal evolution of leukemia cells by applying traditional bulk sequencing techniques, thus preventing a deep understanding of the mechanisms of leukemia development and the identification of potential therapeutic targets. However, with the development and application of single-cell sequencing technology, it is now possible to investigate the gene expression profile, mutations, and epigenetic features of leukemia at the single-cell level, thus providing a new perspective for leukemia research. In this article, we review the recent applications and advances of single-cell sequencing technology in leukemia research, discuss its potential for enhancing our understanding of the mechanisms of leukemia development, discovering therapeutic targets and personalized treatment, and provide reference guidelines for the significance of this technology in clinical research.

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SCP4-STK35/PDIK1L complex is a dual phospho-catalytic signaling dependency in acute myeloid leukemia

Abstract: Highlights d Phosphatase-domain-focused CRISPR screening applied to cancer cell lines d SCP4 phosphatase is an acquired catalytic dependency in AML d STK35/PDIK1L kinases bind to the catalytically active SCP4

Cited by 3 publications

References 88 publications

CTDSPL2 promotes the progression of non-small lung cancer through PI3K/AKT signaling via JAK1

CTDSPL2 promotes the progression of non-small lung cancer through PI3K/AKT signaling via JAK1

CTDSPL2 promotes the progression of non-small lung cancer through PI3K/AKT signaling via JAK1

Application and research progress of single cell sequencing technology in leukemia

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