المؤلفون: Thomas, Liz, Chutani, Namita, R, Krishna, Nair, Asha S., Yellapu, Nanda Kumar, Karyala, Prashanthi, Pakala, Suresh B.

المساهمون: University of Hyderabad

المصدر: Biochemical Journal ; volume 480, issue 20, page 1675-1691 ; ISSN 0264-6021 1470-8728

مصطلحات موضوعية: Cell Biology, Molecular Biology, Biochemistry

الوصف: Although Microrchidia 2 (MORC2) is widely overexpressed in human malignancies and linked to cancer cell proliferation, metabolism, and metastasis, the mechanism of action of MORC2 in cancer cell migration and invasion is yet undeciphered. Here, we identified for the first time that MORC2, a chromatin remodeler, regulates E-cadherin expression and, subsequently regulates breast cancer cell migration and invasion. We observed a negative correlation between the expression levels of MORC2 and E-cadherin in breast cancer. Furthermore, the overexpression of MORC2 resulted in decreased expression levels of E-cadherin. In addition, co-immunoprecipitation and chromatin immunoprecipitation assays revealed that MORC2 interacts with HDAC1 and gets recruited onto the E-cadherin promoter to inhibit its transcription, thereby suppress its expression. Consequently, knockdown of HDAC1 in MORC2-overexpressing cells led to reduced cancer cell migration and invasion. Interestingly, we noticed that MORC2-regulated glucose metabolism via c-Myc, and LDHA, also modulates the expression of E-cadherin. Collectively, these results demonstrate for the first time a mechanistic role for MORC2 as an upstream regulator of E-cadherin expression and its associated functions in breast cancer.

الإتاحة: https://doi.org/10.1042/bcj20230304Test
https://portlandpress.com/biochemj/article-pdf/480/20/1675/950944/bcj-2023-0304.pdfTest

المؤلفون: Patel, Ashish, Rajendran, Malathi, Shah, Ashish, Patel, Harnisha, Pakala, Suresh B., Karyala, Prashanthi

المصدر: Journal of Biomolecular Structure and Dynamics ; volume 40, issue 11, page 5138-5146 ; ISSN 0739-1102 1538-0254

الإتاحة: https://doi.org/10.1080/07391102.2020.1868338Test

المؤلفون: Chutani, Namita, Ragula, Sandhya, Syed, Khajamohiddin, Pakala, Suresh B.

المصدر: Biomolecules (2218-273X); Oct2023, Vol. 13 Issue 10, p1527, 12p

مصطلحات موضوعية: TUMOR suppressor genes, CANCER cell growth, CANCER cell migration, CHROMATIN, ADENOSINE triphosphate, CARCINOGENS, MOLECULAR pathology, CELL migration inhibition

مستخلص: A newly discovered chromatin remodeler, MORC2, is a Microrchidia (MORC) family member. MORC2 acts as a chromatin remodeler by binding to the DNA and changing chromatin conformation using its ATPase domain. MORC2 is highly expressed in a variety of human cancers. It controls diverse signaling pathways essential for cancer development through its target genes and interacting partners. MORC2 promotes cancer cells' growth, invasion, and migration by regulating the expression of genes involved in these processes. MORC2 is localized primarily in the nucleus and is also found in the cytoplasm. In the cytoplasm, MORC2 interacts with adenosine triphosphate (ATP)-citrate lyase (ACLY) to promote lipogenesis and cholesterogenesis in cancer. In the nucleus, MORC2 interacts with the transcription factor c-Myc to control the transcription of genes involved in glucose metabolism to drive cancer cell migration and invasion. Furthermore, MORC2 recruits on to the promoters of tumor suppressor genes to repress their transcription and expression to promote oncogenesis. In addition to its crucial function in oncogenesis, it plays a vital role in DNA repair. Overall, this review concisely summarizes the current knowledge about MORC2-regulated molecular pathways involved in cancer. [ABSTRACT FROM AUTHOR]

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المؤلفون: Guddeti, Rohith Kumar, Pacharla, Himavani, Yellapu, Nanda Kumar, Karyala, Prashanthi, Pakala, Suresh B.

المصدر: Medical Oncology ; volume 40, issue 3 ; ISSN 1559-131X

مصطلحات موضوعية: Cancer Research, Oncology, Hematology, General Medicine

الإتاحة: https://doi.org/10.1007/s12032-023-01974-2Test

المؤلفون: Chalakur-Ramireddy, Naveen K.R., Pakala, Suresh B.

المصدر: Bioscience Reports ; volume 38, issue 1 ; ISSN 0144-8463 1573-4935

الوصف: TNBC (Triple Negative Breast Cancer) is a subtype of breast cancer with an aggressive phenotype which shows high metastatic capability and poor prognosis. Owing to its intrinsic properties like heterogeneity, lack of hormonal receptors and aggressive phenotype leave chemotherapy as a mainstay for the treatment of TNBC. Various studies have demonstrated that chemotherapy alone or therapeutic drugs targeting TNBC pathways, epigenetic mechanisms and immunotherapy alone have not shown significant improvement in TNBC patients. On the other hand, a combination of therapeutic drugs or addition of chemotherapy with therapeutic drugs has shown substantial improvement in results and proven to be an effective strategy for TNBC treatment. This review sheds light on effective combinational drug strategies and current clinical trial status of various combinatorial drugs for the treatment of TNBC.

الإتاحة: https://doi.org/10.1042/bsr20171357Test

المؤلفون: Pakala, Suresh B., Bui-Nguyen, Tri M., Reddy, Sirigiri Divijendra Natha, Li, Da-Qiang, Peng, Shaohua, Rayala, Suresh K., Behringer, Richard R., Kumar, Rakesh

المصدر: Journal of Biological Chemistry ; volume 292, issue 11, page 4764 ; ISSN 0021-9258

مصطلحات موضوعية: Cell Biology, Molecular Biology, Biochemistry

الإتاحة: https://doi.org/10.1074/jbc.a117.139469Test
https://api.elsevier.com/content/article/PII:S0021925820521996?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S0021925820521996?httpAccept=text/plainTest

المؤلفون: Bui-Nguyen, Tri M., Pakala, Suresh B., Sirigiri, Divijendranatha Reddy, Martin, Emil, Murad, Ferid, Kumar, Rakesh

المصدر: Journal of Biological Chemistry ; volume 292, issue 11, page 4765 ; ISSN 0021-9258

مصطلحات موضوعية: Cell Biology, Molecular Biology, Biochemistry

الإتاحة: https://doi.org/10.1074/jbc.a117.065987Test
https://api.elsevier.com/content/article/PII:S002192582052200X?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S002192582052200X?httpAccept=text/plainTest

المؤلفون: Saravanan, Roshni, Balasubramanian, Vaishnavi, Swaroop Balamurugan, Srikanth Swamy, Ezhil, Inemai, Afnaan, Zeba, John, Jisha, Sundaram, Sandhya, Gouthaman, Shanmugasundaram, Pakala, Suresh B., Rayala, Suresh Kumar, Venkatraman, Ganesh

المصدر: Journal of Cellular Physiology ; volume 237, issue 11, page 4132-4156 ; ISSN 0021-9541 1097-4652

الوصف: Breast cancer is one of the leading causes contributing to the global cancer burden. The triple negative breast cancer (TNBC) molecular subtype accounts for the most aggressive type. Despite progression in therapeutic options and prognosis in breast cancer treatment options, there remains a high rate of distant relapse. With advancements in understanding the role of zinc and zinc carriers in the prognosis and treatment of the disease, the scope of precision treatment/targeted therapy has been expanded. Zinc levels and zinc transporters play a vital role in maintaining cellular homeostasis, tumor surveillance, apoptosis, and immune function. This review focuses on the zinc transporter, LIV1, as an essential target for breast cancer prognosis and emerging treatment options. Previous studies give an insight into the role of LIV1 in fulfilling the most important hallmarks of cancer such as apoptosis, metastasis, invasion, and evading the immune system. Normal tissue expression of LIV1 is limited. Higher expression of LIV1 has been linked to Epithelial‐Mesenchymal Transition, histological grade of cancer, and early node metastasis. LIV1 was found to be one of the attractive targets in the therapeutic hunt for TNBCs. TNBCs are an immunogenic breast cancer subtype. As zinc transporters are known to serve as the metabolic gatekeepers of immune cells, this review bridges tumor infiltrating lymphocytes, TNBC and LIV1. In addition, the suitability of LIV1 as an antibody‐drug conjugate (Seattle genetics [SGN]‐LIV1A) target in TNBC, represents a promising strategy for patients. Early clinical trial results reveal that this novel agent reduces tumor burden by inducing mitotic arrest, immunomodulation, and immunogenic cell death, warranting further investigation of SGN‐LIV1A in combination with immuno‐oncology agents. Priming the patient's immune response in combination with SGN‐LIV1A could eventually change the landscape for the TNBC patient population.

الإتاحة: https://doi.org/10.1002/jcp.30880Test

المؤلفون: Vattem, Chaitanya, Pakala, Suresh B

المصدر: Journal of Biosciences ; volume 47, issue 2 ; ISSN 0973-7138

مصطلحات موضوعية: General Agricultural and Biological Sciences, General Biochemistry, Genetics and Molecular Biology, General Medicine

الإتاحة: https://doi.org/10.1007/s12038-022-00263-wTest

المؤلفون: Saroha, Himanshu Singh, Kumar Guddeti, Rohith, Jacob, Jasmine P., Kumar Pulukuri, Kiran, Karyala, Prashanthi, Pakala, Suresh B.

المصدر: Medical Oncology ; volume 39, issue 9 ; ISSN 1559-131X

مصطلحات موضوعية: Cancer Research, Oncology, Hematology, General Medicine

الإتاحة: https://doi.org/10.1007/s12032-022-01728-6Test