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: Guddeti, Rohith Kumar, Thomas, Liz, Kannan, Anbarasu, Karyala, Prashanthi, Pakala, Suresh B.

المساهمون: Nebreda, Angel

المصدر: FEBS Letters ; volume 595, issue 9, page 1289-1302 ; ISSN 0014-5793 1873-3468

الوصف: Microrchidia family CW‐type zinc finger 2 (MORC2) is a recently identified chromatin modifier with an emerging role in cancer metastasis. However, its role in glucose metabolism, a hallmark of malignancy, remains to be explored. We found that MORC2 is a glucose‐inducible gene and a target of c‐Myc. Our meta‐analysis revealed that MORC2 expression is positively correlated with the expression of enzymes involved in glucose metabolism in breast cancer patients. Furthermore, overexpression of MORC2 in MCF‐7 and BT‐549 cells augmented the expression and activity of a key glucose metabolism enzyme, lactate dehydrogenase A (LDHA). Conversely, selective knockdown of MORC2 by siRNA markedly decreased LDHA expression and activity and in turn reduced cancer cell migration. Collectively, these findings provide evidence that MORC2, a glucose‐inducible gene, modulates the migration of breast cancer cells through the MORC2–c‐Myc–LDHA axis.

الإتاحة: https://doi.org/10.1002/1873-3468.14062Test

المؤلفون: Kumar, Anupam, Molli, Poonam R., Pakala, Suresh B., Nguyen, Tri M. Bui, Rayala, Suresh K., Kumar, Rakesh

المصدر: Journal of Cellular Biochemistry ; volume 107, issue 4, page 579-585 ; ISSN 0730-2312 1097-4644

الوصف: The p21‐activated kinases (PAKs) are signaling nodes that play a crucial role in cellular processes including cell motility, differentiation, survival, gene transcription, and hormone signaling. PAKs are highly conserved family of serine–threonine kinases that act as effector for small GTPases Rac and Cdc42. Most of our knowledge about PAK functions has been derived from genetic approaches in lower organisms and many of these functions are similar to that seen in mammalian cells. In this review, we have summarized the extensive information generated in lower eukaryotes and very briefly discussed the current status of PAKs in humans. J. Cell. Biochem. 107: 579–585, 2009. © 2009 Wiley‐Liss, Inc.

الإتاحة: https://doi.org/10.1002/jcb.22159Test