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

المصدر: Medical Oncology; Mar2023, Vol. 40 Issue 3, p1-11, 11p

مستخلص: Cancer cell proliferation is a high energy demanding process, where the cancer cells acquire energy by high rates of glycolysis, and this phenomenon is known as the "Warburg effect". Microrchidia 2 (MORC2), an emerging chromatin remodeler, is over expressed in several cancers including breast cancer and found to promote cancer cell proliferation. However, the role of MORC2 in glucose metabolism in cancer cells remains unexplored. In this study, we report that MORC2 interacts indirectly with the genes involved in glucose metabolism via transcription factors MAX (MYC-associated factor X) and MYC. We also found that MORC2 co-localizes and interacts with MAX. Further, we observed a positive correlation of expression of MORC2 with glycolytic enzymes Hexokinase 1 (HK1), Lactate dehydrogenase A (LDHA) and Phosphofructokinase platelet (PFKP) type in multiple cancers. Surprisingly, the knockdown of either MORC2 or MAX not only decreased the expression of glycolytic enzymes but also inhibited breast cancer cell proliferation and migration. Together, these results demonstrate the involvement of the MORC2/MAX signaling axis in the expression of glycolytic enzymes and breast cancer cell proliferation and migration. [ABSTRACT FROM AUTHOR]

: Copyright of Medical Oncology is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

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; Nov2022, Vol. 237 Issue 11, p4132-4156, 25p

مصطلحات موضوعية: TRIPLE-negative breast cancer, ZINC transporters, TUMOR-infiltrating immune cells, BREAST cancer prognosis, PROGNOSIS

مستخلص: 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. [ABSTRACT FROM AUTHOR]

: Copyright of Journal of Cellular Physiology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: Chalakur-Ramireddy, Naveen K. R.¹, Pakala, Suresh B.¹ pakalasb@iisertirupati.ac.in

المصدر: Bioscience Reports. 2/28/2018, Vol. 38 Issue 1, p1-14. 14p.

مصطلحات موضوعية: *TRIPLE-negative breast cancer, *BREAST cancer, *CANCER chemotherapy, *DRUGS, *CANCER

مستخلص: 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. [ABSTRACT FROM AUTHOR]

المؤلفون: Reddy, Sirigiri Divijendra Natha¹, Pakala, Suresh B.¹, Molli, Poonam R.¹, Sahni, Neil¹, Karanam, Narasimha Kumar¹, Mudvari, Prakriti¹, Kumar, Rakesh¹ bcmrxk@gwu.edu

المصدر: Journal of Biological Chemistry. 8/10/2012, Vol. 287 Issue 33, p27843-27850. 8p.

مصطلحات موضوعية: *METASTASIS, *CANCER invasiveness, *BREAST cancer, *GENE expression, *TUMOR suppressor genes

مستخلص: Metastasis-associated protein 1 (MTA1) is widely overexpressed in human cancers and is associated with malignant phenotypic changes contributing to morbidity in the associated diseases. Here we discovered for the first time that MTA1, a master chromatin modifier, transcriptionally represses the expression of phosphatase and tensin homolog (PTEN), a tumor suppressor gene, by recruiting class II histone deacetylase 4 (HDAC4) along with the transcription factor Yin-Yang 1 (YY1) onto the PTEN promoter. We also found evidence of an inverse correlation between the expression levels of MTA1 and PTEN in physiologically relevant breast cancer microarray datasets.Wefound that MTA1 up-regulation leads to a decreased expression of PTEN protein and stimulation of PI3K as well as phosphorylation of its signaling targets. Accordingly, selective down-regulation of MTA1 in breast cancer cells increases PTEN expression and inhibits stimulation of the PI3K/AKT signaling. Collectively, these findings provide a mechanistic role for MTA1 in transcriptional repression of PTEN, leading to modulation of the resulting signaling pathways. [ABSTRACT FROM AUTHOR]

المؤلفون: Guddeti, Rohith Kumar¹ (AUTHOR), Bali, Prerna¹ (AUTHOR), Karyala, Prashanthi² (AUTHOR), Pakala, Suresh B.¹ (AUTHOR) pakalasb@iisertirupati.ac.in

المصدر: Biochemical & Biophysical Research Communications. Nov2019, Vol. 520 Issue 1, p54-59. 6p.

مصطلحات موضوعية: *BREAST cancer, *GLUCOSE metabolism, *CELL motility, *CELL migration, *CHROMATIN

مستخلص: Metastasis Associated Protein1 (MTA1) is a chromatin modifier and its expression is significantly associated with prognosis of many cancers. However, its role in glucose metabolism remains unexplored. Here, we report that MTA1 has a significant role in glucose metabolism where MTA1 regulates the LDHA expression and activity and subsequently its function in breast cancer motility. The results showed that MTA1 expression is positively correlated with the LDHA expression levels in breast cancer patients. Further, it was found that MTA1 is necessary for the optimal expression of LDHA. The underlying molecular mechanism involves the interaction of MTA1 with c-Myc and recruitment of MTA1-c-Myc complex on to the LDHA promoter to regulate its transcription. Consequently, the LDHA knock down using LDHA specific siRNA in MCF7 cells stably expressing MTA1 reduced the migration of MCF7 cells. Altogether these findings revealed the regulatory role for MTA1 in LDHA expression and its resulting biological function. • MTA1 interacts with the genes of glucose metabolism. • MTA1 regulates LDHA expression and its activity. • MTA1 interacts with c-Myc. • LDHA mediates MTA1 mediated cell motility. [ABSTRACT FROM AUTHOR]