Review
Oncology
Alakananda Basu, Christoffer Briggs Lambring
Summary: This article discusses the importance of breast cancer in women in the United States and the role of Akt isoforms in the development of breast cancer. While Akt isoforms share similar structures, they exhibit redundant, distinct, and opposite functions in breast cancer. Understanding the isoform-specific function of Akt is critical for effectively targeting the Akt signaling pathway in cancer therapy.
Article
Biochemistry & Molecular Biology
Crina E. Tiron, Emilia Patrascanu, Paula A. Postu, Irina C. Vacarean Trandafir, Adrian Tiron, Ioana Grigoras
Summary: This study demonstrated that exposure of TNBC cells to sevoflurane resulted in morphological and behavioral changes, as well as differential regulation of AKT isoforms, especially early upregulation of AKT3. Treatment with sevoflurane at specific time points and concentrations significantly increased cell viability, proliferation, aggressiveness, and expression of vimentin and HIF.
CURRENT ISSUES IN MOLECULAR BIOLOGY
(2021)
Article
Oncology
Bo Ma, Hanshuang Shao, Xia Jiang, Zhou Wang, Chuanyue (Cary) Wu, Diana Whaley, Alan Wells
Summary: The study revealed that the activation of Akt1/2 isoforms induced by E-cadherin was the essential mechanism of chemoresistance, while Akt3 made cells more fragile.
CANCER BIOLOGY & MEDICINE
(2022)
Review
Immunology
Mireia Guerau-de-Arellano, Zayda L. L. Piedra-Quintero, Philip N. Tsichlis
Summary: Akt, a PI3K-activated serine-threonine kinase, plays important roles in immune cell development and effector functions in both innate and adaptive immune cells.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Eros Azzalini, Domenico Tierno, Michele Bartoletti, Renzo Barbazza, Giorgio Giorda, Fabio Puglisi, Sabrina Chiara Cecere, Nunzia Simona Losito, Daniela Russo, Giorgio Stanta, Vincenzo Canzonieri, Serena Bonin
Summary: New therapeutical strategies are needed to improve survival in high-grade serous ovarian cancer patients. AKT inhibitors, when used in combination with PARP inhibitors and platinum-based therapies, show promise as a treatment option. However, it is still unclear which subgroup of patients would benefit the most from this approach. This study analyzes the expression of AKT isoforms in a retrospective cohort and identifies four AKT expression groups that are associated with patients' survival, tumor morphology, and BRCA status. The findings help in stratifying patients for future clinical trials and provide insights into the potential of AKT and PARP inhibitors therapy.
Review
Medicine, Research & Experimental
Sofia M. Tarchi, Monica Pernia Marin, Md. Murad Hossain, Mary Salvatore
Summary: Breast density has been consistently linked to increased risk of breast cancer over the past five decades. Mammographically dense breasts, categorized as heterogeneously dense and extremely dense according to the BI-RADS system, show a significant correlation with greater glandular tissue alone. However, the correlation is weak. While the underlying mechanisms behind breast density-related tumor initiation and progression remain unknown, evidence suggests that molecular pathways involved in epithelial-stromal interactions may contribute to collagen deposition, increased matrix stiffness, and cell migration, thus promoting breast density and carcinogenesis. This article explores these molecular mechanisms as potential contributors to breast density-related cancer.
JOURNAL OF TRANSLATIONAL MEDICINE
(2023)
Article
Oncology
Yueting Peng, Zhongyuan Chen, Yuchen He, Ping Li, Yu Chen, Xiangyan Chen, Ying Jiang, Xiang Qin, Shun Li, Tingting Li, Chunhui Wu, Hong Yang, Fengming You, Yiyao Liu
Summary: The study found that NMIIA plays a role in establishing cell polarity, while NMIIB is involved in generating traction force and polarized distribution, depending on substrate stiffness. Substrate stiffness modulates the distribution and activation of NMII isoforms through multiple signaling pathways and kinase-specific phosphoregulation.
Article
Multidisciplinary Sciences
Jagadish C. Ghosh, Michela Perego, Ekta Agarwal, Irene Bertolini, Yuan Wang, Aaron R. Goldman, Hsin-Yao Tang, Andrew Kossenkov, Catherine J. Libby, Lucia R. Languino, Edward F. Plow, Annamaria Morotti, Luisa Ottobrini, Marco Locatelli, David W. Speicher, M. Cecilia Caino, Joel Cassel, Joseph M. Salvino, Marie E. Robert, Valentina Vaira, Dario C. Altieri
Summary: The study reveals that many human tumors have reduced levels of Mic60, an essential scaffold of mitochondrial structure, which leads to the disruption of mitochondrial integrity. Surprisingly, these tumors show decreased cell proliferation, resistance to cell death, and activation of a gene expression program related to innate immunity and cytokine/chemokine signaling. This process induces epithelial-mesenchymal transition, tumor cell movement, and promotes metastatic dissemination.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Monika Mlinaric, Ivan Lucic, Lidija Milkovic, Ines V. da Silva, Ivana Tartaro Bujak, Vesna Musani, Graca Soveral, Ana Cipak Gasparovic
Summary: Aquaporin 3 (AQP3) is a membrane protein that transports hydrogen peroxide, water, and glycerol. It is implicated in tumor progression and malignancy in breast cancer and may be a target for therapy. This study examined the relationship between AQP3 expression, disruption of lipid raft harboring EGFR, and the EGFR/PI3K/Akt signaling pathway in breast cancer cell lines. The results indicate that AQP3 may not directly affect the PI3K/Akt pathway but rather its role is cell-line specific.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Multidisciplinary
Yerbol Tagay, Sina Kheirabadi, Zaman Ataie, Rakesh K. Singh, Olivia Prince, Ashley Nguyen, Alexander S. Zhovmer, Xuefei Ma, Amir Sheikhi, Denis Tsygankov, Erdem D. Tabdanov
Summary: The principal cause of death in cancer patients is metastasis, which is conventionally linked to actomyosin-driven cell locomotion. However, this study identifies a complementary mechanism of metastatic locomotion powered by dynein-generated forces. These findings provide new insights into the fundamental understanding of cell locomotion mechanisms and expand the spectrum of clinical targets against metastasis.
Review
Cell Biology
Kunrui Zhu, Yanqi Wu, Ping He, Yu Fan, Xiaorong Zhong, Hong Zheng, Ting Luo
Summary: Phosphatidylinositol 3-kinase (PI3K), protein kinase B (PKB/AKT) and mechanistic target of rapamycin (mTOR) (PAM) pathways play important roles in breast tumorigenesis and offer potential targets for cancer therapy.
Article
Immunology
Rajeev Dhupar, Katherine E. Jones, Amy A. Powers, Seth H. Eisenberg, Kai Ding, Fangyuan Chen, Cecile Nasarre, Zhanpeng Cen, Yi-Nan Gong, Amanda C. LaRue, Elizabeth S. Yeh, James D. Luketich, Adrian V. Lee, Steffi Oesterreich, Michael T. Lotze, Robert M. Gemmill, Adam C. Soloff
Summary: Tumor-associated macrophages (TAMs) play a significant role in breast cancer progression, and the neuropilin-2 (NRP2) isoforms NRP2a and NRP2b have been found to regulate TAM functionality. The expression levels of NRP2a and NRP2b in TAMs are influenced by the location of the tumor, and they are closely associated with TAM infiltration in both primary and metastatic breast cancers. This study also demonstrates that NRP2a and NRP2b have distinct functionality in macrophages and are associated with different TAM subsets in breast cancer.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Ru Wang, Ines Godet, Yongkang Yang, Shaima Salman, Haiquan Lu, Yajing Lyu, Qiaozhu Zuo, Yufeng Wang, Yayun Zhu, Chelsey Chen, Jianjun He, Daniele M. Gilkes, Gregg L. Semenza
Summary: This study discovered that HIFs induce the expression of ADAM12, leading to EGFR signaling activation and subsequently promoting breast cancer cell migration, invasion, and metastasis. Inhibition of ADAM12 expression or activity can effectively reduce tumor cell migration, invasion, and lung metastasis.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Pharmacology & Pharmacy
Federica Martorana, Gianmarco Motta, Giuliana Pavone, Lucia Motta, Stefania Stella, Silvia Rita Vitale, Livia Manzella, Paolo Vigneri
Summary: The AKT protein kinase is crucial in breast cancer treatment, especially in resistant subtypes. Several AKT inhibitors are in clinical trials, with new combination strategies being explored to enhance therapeutic efficacy.
FRONTIERS IN PHARMACOLOGY
(2021)
Review
Oncology
Huayi Li, Lorenzo Prever, Emilio Hirsch, Federico Gulluni
Summary: The PI3K signaling pathway is crucial in breast cancer and inhibitors targeting this pathway show promising activity, but resistance and adverse reactions limit their efficacy. Combination therapies and identifying suitable patient subpopulations are needed to enhance therapeutic benefit.