Objective: To investigate the expression and relationship of activated Cdc42-associated kinase 1 (ACK1) and the clinical characteristics of esophageal squamous cell carcinoma (ESCC).
Methods: The ACK1 expression in ESCC cell lines was detected by Western blot. Immunohistochemistry was performed to assay the expression level of ACK1 protein in tumor tissues and adjacent normal epithelium from 105 ESCC patients in tissue microarray and 45 patients in normal tissue slices. Semi-quantitative RT-PCR(reverse transcription-polymerase chain reaction)was performed to determine the expression level of ACK1 mRNA in 45 pairs of ESCC frozen tissues.
Results: The expression level of ACK1 protein was significantly up-regulated in 48.6% ESCC tissues as compared with the normal adjacent epithelium in tissue microarray. The overexpression of ACK1 was significantly correlated with the lymph node metastasis and TNM stage of ESCC patients. The results of normal tissue slices were consistent with those of tissue microarray. Furthermore the overexpression of ACK1 was associated with a poor survival of ESCC patients (P = 0.030). The elevated mRNA level of ACK1 in ESCC tissues was correlated with the lymph node metastasis and TNM stage of ESCC patients. And a significant correlation was observed between protein and mRNA level of ACK1 (P = 0.021).
Conclusion: The up-regulated expressions of ACK1 protein and mRNA are correlated with the progression and prognosis of ESCC.
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Curr Issues Mol Biol
October 2024
Household & Health Care (LG H&H) R&D Center, 70, Magokjoongang 10-ro, Gangseo-gu, Seoul 07795, Republic of Korea.
Nat Commun
July 2024
Department of Surgery, Washington University in St Louis, St Louis, MO, 63110, USA.
Mutations that decrease or increase the activity of the tyrosine phosphatase, SHP2 (encoded by PTPN11), promotes developmental disorders and several malignancies by varying phosphatase activity. We uncovered that SHP2 is a distinct class of an epigenetic enzyme; upon phosphorylation by the kinase ACK1/TNK2, pSHP2 was escorted by androgen receptor (AR) to chromatin, erasing hitherto unidentified pY54-H3 (phosphorylation of histones H3 at Tyr54) epigenetic marks to trigger a transcriptional program of AR. Noonan Syndrome with Multiple Lentigines (NSML) patients, SHP2 knock-in mice, and ACK1 knockout mice presented dramatic increase in pY54-H3, leading to loss of AR transcriptome.
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June 2023
Department of Surgery, Cancer Research Building, Washington University in St Louis, 660 Euclid Ave., St Louis, MO, 63110, USA.
The testicular androgen biosynthesis is well understood, however, how cancer cells gauge dwindling androgen to dexterously initiate its de novo synthesis remained elusive. We uncover dual-phosphorylated form of sterol regulatory element-binding protein 1 (SREBF1), pY673/951-SREBF1 that acts as an androgen sensor, and dissociates from androgen receptor (AR) in androgen deficient environment, followed by nuclear translocation. SREBF1 recruits KAT2A/GCN5 to deposit epigenetic marks, histone H2A Lys130-acetylation (H2A-K130ac) in SREBF1, reigniting de novo lipogenesis & steroidogenesis.
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July 2023
Laboratory Center, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, 274 Middle Zhijiang Road, Shanghai 200071, China; Cancer Institute, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China. Electronic address:
Rhizoma Paridis is a traditional Chinese medicine commonly used for treatment of malignant tumors. Paris saponins Ⅶ (PSⅦ) is one of the components of Rhizoma Paridis, but the role of PSⅦ in glucose metabolism in ovarian cancer remains elucidated. A series of experiments in the current study demonstrated that PSⅦ inhibites glycolysis and promotes cell apoptosis in ovarian cancer cells.
View Article and Find Full Text PDFMol Med
January 2023
Department of Thoracic Surgery, Harbin Medical University Cancer Hospital, 150 Haping Road, Harbin, 150040, Heilongjiang, China.
Background: Activated Cdc42-associated kinase 1 (ACK1) is a promising druggable target for cancer, but its inhibitors only showed moderate effects in clinical trials. The study aimed to investigate the underlying mechanisms and improve the antitumor efficacy of ACK1 inhibitors.
Methods: RNA-seq was performed to determine the downstream pathways of ACK.
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