A novel cancer testis antigen target A-kinase anchor protein (AKAP4) for the early diagnosis and immunotherapy of colon cancer

Jagadish, Nirmala; Parashar, Deepak; Gupta, Namita; Agarwal, Sumit; Sharma, Aditi; Fatima, Rukhsar; Suri, Vaishali; Kumar, Rajive; Gupta, Anju; Lohiya, N. K.; Suri, Anil

doi:10.1080/2162402x.2015.1078965

Cited by 21 publications

(14 citation statements)

References 25 publications

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“…Majority of EOC are diagnosed at advanced stage with poor prognosis and high morbidity [ 1 ]. Earlier we reported a novel molecule A kinase anchor protein 4 (AKAP4) [ 20 ] and showed its association with variety of malignancies [ 6 – 9 ]. In present study we investigated the role of AKAP4 in various malignant properties in ovarian cancer cells in vitro and in in vivo ovarian cancer xenograft mouse model.…”

Section: Discussionmentioning

confidence: 99%

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Role of A-Kinase anchor protein (AKAP4) in growth and survival of ovarian cancer cells

2017

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Ovarian cancer represents one of the most common malignancies among women with very high mortality rate worldwide. A-kinase anchor protein 4 (AKAP4), a unique cancer testis (CT) antigen has been shown to be associated with various malignant properties of cancer cells. However, its involvement in various molecular pathways in ovarian cancer remains unknown. In present investigation, employing gene silencing approach, we examined the role of AKAP4 in cell cycle, apoptosis and epithelial-mesenchymal transition (EMT). Further, we also investigated the effect of ablation of AKAP4 on tumor growth in SCID mice ovarian cancer xenograft mouse model. Our results showed that ablation of AKAP4 resulted in increased reactive oxygen species (ROS) generation, DNA damage, cell cycle arrest and apoptosis in ovarian cancer cells. AKAP4 knockdown lead to degradation of protien kinase A (PKA) which was rescued by proteosome inhibitor MG-132. ROS quencher N-acetyl cysteine (NAC) treatment rescued cell cycle arrest and resumed cell division. Subsequently, increased expression of pro-apoptotic molecules and decreased expression of pro-survival/anti-apoptotic factors was observed. As a result of AKAP4 depletion, DNA damage response proteins p-γH2AX, p-ATM and p21 were upregulated. Also, knockdown of CREB resulted in similar findings. Further, PKA inhibitor (H89) and oxidative stress resulted in similar phenotype of ovarian cancer cells as observed in AKAP4 ablated cells. Collectively, for the first time our data showed the involvement of AKAP4 in PKA degradation and perturbed signaling through PKA-CREB axis in AKAP4 ablated ovarian cancer cells.

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Section: Discussionmentioning

confidence: 99%

“…Earlier, we reported a novel CT antigen namely A kinase anchor protein (AKAP4) expression in various types of malignancies [ 6 – 9 ]. It has been proposed that AKAP4 functions as a scaffolding protein and tethers protein kinase A (PKA) in various signaling complexes and subcellular organelles [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

Role of A-Kinase anchor protein (AKAP4) in growth and survival of ovarian cancer cells

2017

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“…Экспрессия гена AKAP4 при различных стадиях и гистотипах КРР была обнаружена у большинства пациентов (84%). Интересно отметить, что экспрессия гена AKAP4 достоверно ассоциировалась (p <0,026) с поздними стадиями (III и IV) у пациентов с КРР, что указывает на его потенциальную роль в агрессивном поведении опухоли [23].…”

Section: рис 2 экспрессия генов Ctage1b Magea1 и Kif2c в здоровых unclassified

Cancer-Testis Antigens in Colon Tumors Diagnostics

Soldatova¹,

Кутилин²,

Vodolazhskiy³

2018

СПНО (MPSE)

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Поиск предиктивных диагностических маркеров рака толстой кишки является актуальной задачей. В данном обзоре рассмотрены современные данные о возможности использования раково-тестикулярных антигенов в диагностике опухолей толстой кишки. Подробно описаны современная классификация раково-тестикулярных антигенов и их наиболее изученные семейства, механизмы регуляции экспрессии, особенности экспрессии некоторых раково-тестикулярных генов (AKAP, OY-TES-1, NY-ESO-1, MAGE-A3, TSP50, SPAG9, PLAC1, GAGE, CTAG2 и др.) при раке толстой кишки и связь с развитием метастазов. Проведен сравнительный анализ в базе BioGPS данных об экспрессии некоторых раково-тестикулярных антигенов в тканях человека. Несмотря на многочисленные исследования экспрессии раково-тестикулярных антигенов в опухолях различных локализаций, их транскрипционная активность при раке толстой кишки остается недостаточно изученной, хотя отдельные представители разных семейств раково-тестикулярных антигенов всё же обладают большим потенциалом в диагностике опухолей данной нозологии. Ключевые слова: раково-тестикулярные антигены, рак толстой кишки, экспрессия генов, онкомаркеры. CANCER-TESTIS ANTIGENS IN COLON TUMORS DIAGNOSTICS

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“…An immunoreactivity score (IRS) was calculated by the product of the percentage of positive cells (PP score) and the intensity of staining (SI score): IRS=PP × SI. IRS >4 was defined as high expression, whereas IRS ≤4 was defined as low expression ( 9 ). Expression of nm23 was observed in cytoplasm, according to SI score: ≥2 represented high expression, while <2 represented low expression.…”

Section: Methodsmentioning

confidence: 99%

Correlation between ultrasonic features and expression levels of C-erbB-2, VEGF and nm23 in breast cancer

et al. 2018

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Breast cancer is one of the most common female malignancies in clinical practice, which ranks number one in terms of its high incidence. We investigated the relevance of ultrasonic features of breast cancer and expression levels of C-erbB-2, vascular endothelial growth factor (VEGF) and nm23 and its clinical significance. A total of 76 patients with breast cancer were recruited who were admitted to The Affiliated Hospital of Qingdao University from January, 2016 to August, 2017. All patients underwent color Doppler ultrasonic imaging, and expression levels of C-erbB-2, VEGF and nm23 in their tumor tissues were measured by immunohistochemistry. The ultrasonic features were evaluated and compared with the expression levels of C-erbB-2, VEGF and nm23 for each patient. Ultrasonography showed a tumor mass with spiculated margins, abnormal vasculature, and a diameter no less than 3 cm, as well as lymph node metastasis. The above signs were associated with high expression of C-erbB-2, VEGF and nm23 (p<0.05), but calcification was not associated with high expression of these biomarkers (p>0.05). For patients with highly expressed C-erbB-2 and VEGF, the time to peak (TTP) of the time-intensity curve obtained by contrast enhanced ultrasound was shorter, while the peak intensity (PI) was higher. On the contrary, for patients with highly expressed nm23, the TTP was apparently longer, while the PI was lower (p<0.05). The ultrasonic features of breast cancer were relevant to the expression levels of C-erbB-2, VEGF and nm23. Thus, the expression levels of C-erbB-2, VEGF and nm23 were predictable indirectly according to the ultrasonic features of the patient, which can be used as a reference for breast cancer treatment and prognosis prediction.

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A novel cancer testis antigen target A-kinase anchor protein (AKAP4) for the early diagnosis and immunotherapy of colon cancer

Cited by 21 publications

References 25 publications

Role of A-Kinase anchor protein (AKAP4) in growth and survival of ovarian cancer cells

Role of A-Kinase anchor protein (AKAP4) in growth and survival of ovarian cancer cells

Cancer-Testis Antigens in Colon Tumors Diagnostics

Correlation between ultrasonic features and expression levels of C-erbB-2, VEGF and nm23 in breast cancer

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