ArticleJournal of experimental & clinical cancer research : CR2015
A-kinase anchor protein 4 (AKAP4) a promising therapeutic target of colorectal cancer.
Article in Journal of experimental & clinical cancer research : CR, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 42 citations in OpenAlex.
- Protein kinase A and local signaling in cancer.The Biochemical journal · 2024Review
- Up-regulation of collagen type V alpha 2 (Open medicine (Warsaw, Poland) · 2023Article
- Current Progress of EMT: A New Direction of Targeted Therapy for Colorectal Cancer with Invasion and Metastasis.Biomolecules · 2022Review
- Silencing of A-kinase anchor protein 4 inhibits the metastasis and growth of non-small cell lung cancer.Bioengineered · 2022Article
- High AKAP8L expression predicts poor prognosis in esophageal squamous cell carcinoma.Cancer cell international · 2022Article
- Patient-Derived Ovarian Cancer Spheroids Rely on PI3K-AKT Signaling Addiction for Cancer Stemness and Chemoresistance.Cancers · 2022Article
- scFv6.C4 DNA vaccine with fragment C of tetanus toxin increases protective immunity against CEA-expressing tumor.Gene therapy · 2021Article
- Targeted biologic inhibition of both tumor cell-intrinsic and intercellular CLPTM1L/CRR9-mediated chemotherapeutic drug resistance.NPJ precision oncology · 2021Article
- LNC473 Regulating APAF1 IRES-Dependent Translation via Competitive Sponging miR574 and miR15b: Implications in Colorectal Cancer.Molecular therapy. Nucleic acids · 2020Article
- Targeting P4HA1 with a Small Molecule Inhibitor in a Colorectal Cancer PDX Model.Translational oncology · 2020Article
- Nuclear-localized costimulatory molecule 4-1BBL promotes colon cancer cell proliferation and migration by regulating nuclear Gsk3β, and is linked to the poor outcomes associated with colon cancer.Cell cycle (Georgetown, Tex.) · 2020Article
- ZEB1-AS1/miR-133a-3p/LPAR3/EGFR axis promotes the progression of thyroid cancer by regulating PI3K/AKT/mTOR pathway.Cancer cell international · 2020Article
- miRNA551b-3p Activates an Oncostatin Signaling Module for the Progression of Triple-Negative Breast Cancer.Cell reports · 2019Article
- ERCC6L promotes cell growth and invasion in human colorectal cancer.Oncology letters · 2019Article
- Aberrantly Expressed Genes and miRNAs in Slow Transit Constipation Based on RNA-Seq Analysis.BioMed research international · 2018Article
- Role of A-Kinase anchor protein (AKAP4) in growth and survival of ovarian cancer cells.Oncotarget · 2017Article
- Silencing of A-Kinase Anchor Protein 4 (AKAP4) Inhibits Proliferation and Progression of Thyroid Cancer.Oncology research · 2017Article
- Combinatorial effect of curcumin with docetaxel modulates apoptotic and cell survival molecules in prostate cancer.Frontiers in bioscience (Elite edition) · 2017Article
- Heat shock protein 70-2 (HSP70-2) a novel cancer testis antigen that promotes growth of ovarian cancer.American journal of cancer research · 2017Article
- Sperm-associated antigen 9 (SPAG9) promotes the survival and tumor growth of triple-negative breast cancer cells.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundColorectal cancer (CRC) ranks third among the estimated cancer cases and cancer related mortalities in the Western world. Early detection and efficient therapy of CRC remains a major health challenge. Therefore, there is a need to identify novel tumor markers for early diagnosis and treatment of CRC.
methodsA-kinase anchor protein 4 (AKAP4) gene and protein expression was monitored by quantitative polymerase chain reaction (qPCR), reverse transcription (RT)-PCR and Western blotting in normal colon tissue lysate, normal colon epithelial cells and in colon cancer cell lines viz., Caco-2, COLO205, COLO320DM, HCT-15, HCT116, HT-29, SW480, and SW620. The effect of AKAP4 on cellular growth, migration and invasion abilities was studied using gene silencing approach. The role of AKAP4 in various pathways involved in cell cycle, apoptosis, senescence was investigated in in vitro and in human xenograft mouse model.
resultsOur studies showed that AKAP4 gene and protein expression was expressed in all colon cancer cells while no expression was detectable in normal colon cells. Ablation of AKAP4 led to reduced cellular growth, migration, invasion and increased apoptosis and senescence of CRC cells in in vitro assays and tumor growth in human xenograft mouse. Human colon xenograft studies showed a significant decrease in the levels of cyclins B1, D and E and cyclin dependent kinases such as CDK1, CDK2, CDK4 and CDK6. Interestingly, an up-regulation in the levels of p16 and p21 was also observed. Besides, an increase in the levels of pro-apoptotic molecules AIF, APAF1, BAD, BID, BAK, BAX, PARP1, NOXA, PUMA and cyt-C and Caspase 3, 7, 8 and 9 was also found in cancer cells as well as in xenograft tissue sections. However, anti-apoptotic molecules BCL2, Bcl-xL, cIAP2, XIAP, Axin2 and Survivin were down regulated in these samples. Our data also revealed elevated expression of epithelial marker E-cadherin and down regulation of EMT markers N-cadherin, P-cadherin, SLUG, α-SMA, SNAIL, TWIST and Vimentin. Further ablation of AKAP4 resulted in the down regulation of invasion molecules matrix metalloproteinase MMP2, MMP3 and MMP9.
conclusionAKAP4 appears to be a novel CRC-associated antigen with a potential for developing as a new clinical therapeutic target.
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