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Dissertation Defense: Dynamic integrin expression changes and adhesion-driven mitobiogenesis in ovarian cancer metastasis

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Nazia Bano
Dissertation Defense

Dynamic integrin expression changes and adhesion-driven mitobiogenesis in ovarian cancer metastasis

Nazia Bano

Graduate Student, Translational Biology, Medicine, and Health
Graduate Research Assistant, Schmelz Lab, Department of Human Nutrition, Food, and Exercise 
May 6, at 10 a.m.
Integrated Life Sciences Building (ILSB), Room 1040

About this Dissertation

Ovarian cancer is the 6th leading cause of cancer-related deaths in women, with survival rate of only 31% in metastatic disease. The unique transcoelomic dissemination of ovarian cancer cells include detachment from the primary site, aggregation into multicellular spheroids and attachment and invasion of distant tissues. Successful peritoneal metastasis requires cancer cells to adapt to a changing microenvironment requiring coordinated changes in cell adhesion and mitochondrial function. Prior studies have demonstrated that aggregation promotes survival through fragmentation of mitochondria and reduced metabolic activity, and restoration of mitochondrial structure and metabolism through mitobiogenesis after adhesion to secondary sites. Here, we investigated the role of integrin-mediated adhesion in controlling mitochondrial and metabolic adaptation at the secondary site of adhesion during ovarian cancer dissemination. By modeling the primary adherent, aggregation (spheroid), and adherent spheroid stage under physiologically relevant oxygen and nutrient conditions, we demonstrate that integrin expression is highly dynamic throughout dissemination and are accompanied by coordinated changes of other adhesion molecules, extracellular matrix (ECM) components, and their regulators. Spatial expression analyses revealed that integrins and CD44 exhibit distinct localization patterns within spheroids and were frequently observed in the nucleus, suggesting a novel role in transcriptional regulation that may contribute to survival, cellular plasticity, and metastatic progression. Expression and functional studies identified ITGαVβ1 as key mediators of spheroid adhesion and outgrowth at secondary sites. While mitochondrial activity is suppressed during aggregation, adhesion induces metabolic reprogramming characterized by restoration of mitochondrial function through enhanced mitobiogenesis to support outgrowth, and invasion for successful metastasis. This process is driven by signaling through the ITGαVβ1/FAK pathway. Since pharmacological inhibition of ITGαVβ1 or FAK, reduced mitochondrial mass, decreased membrane potential, oxygen consumption rate, and inhibited or reduced spheroid outgrowth. These findings establish the ITGαVβ1/FAK axis as a central link between adhesion-mediated signaling and mitobiogenesis, and is a promising therapeutic target to limit ovarian cancer metastasis and improve patient outcomes.

More About the Candidate and Project

Education

Virginia Tech, Translational Biology, Medicine, and Health, Ph.D. Candidate

PMAS Arid Agriculture University, M. Phil., Zoology


Karakoram International University, B.S. (Honors)., Zoology

Training

Graduate Research Assistant, Schmelz Lab, Department of Human Nutrition, Food, and Exercise

Mentors

Eva Schmelz, M.S., Ph.D., Professor, Department of Human Nutrition, Food, and Exercise; Principal Scientist, Integrated Life Sciences Building

Committee Members

  • Joshua C. Drake, Ph.D., Assistant Professor, Molecular and Cellular Science, Department of Human Nutrition, Foods, and Exercise
  • Irving Coy Allen, Ph.D., MBA, M.S., Professor, Inflammatory Disease, Department of Biomedical Sciences and Pathobiology; Assistant Head for Research Support, Department of Biomedical Sciences and Pathobiology
  • Joanne Tuohy, DVM, Ph.D., DACVS-Small Animal, Associate Professor and Surgical Oncology, Department of Small Animal Clinical Sciences, Virginia-Maryland College of Veterinary Medicine 

Publications

  • Bano N, Browning JL, Lewis I, Amin M, Zimmerman P, Lee L and Schmelz EM (2026) Dynamic integrin expression, atypical nuclear localization, and spatial distribution during ovarian cancer progression and metastasis. Front. Cell Dev. Biol. 14:1744403. doi: 10.3389/fcell.2026.1744403.


  • Sweet M, Bloomfield M, Keen N, Bano N, Pan X, Baudoin NC, Udayasuryan B, Ahmad RN, Riddervold E, Klaiber E, Verbridge SR, Schmelz EM, Chen J, Cimini D. (2025) Oxidative stress and serum deprivation influence the evolution of newly formed tetraploid cells during tumorigenesis. PNAS. 2025 Sep [accepted].


  • Bloomfield M, Huth S, McCausland D, Saad R, Bano N, Chau TN, Sweet M, Baudoin NC, McCaffrey A, Fluet K, Schmelz EM, Ben-David U, Cimini D. Cell and nuclear size are associated with chromosomal instability and tumorigenicity in cancer cells that undergo whole genome doubling. 2025 Apr 2:2025.03.28.645986. doi: 10.1101/2025.03.28.645986. PMID: 40236241; PMCID: PMC11996335.


  • Grieco JP, Compton SLE, Bano N, Brookover L, Nichenko AS, Drake JC, Schmelz EM. (2023) Mitochondrial plasticity supports proliferative outgrowth and invasion of ovarian cancer spheroids during adhesion. Front Oncol. 2023 Jan 16; 12:1043670.

  • Aziz N, Mehmood A, Jadoon A, Farooq H, Usama T, Ayesha Kazmi S, Gul M, Bano N, Ali S, Zeeshan Malik M, Tahir H, Ishaque Aamir S, khan R, Ahmad J. (2021) Gut Microbiome Association with Chronic Inflammations in COVID-19 Patients. Annals of the Romanian Society for Cell Biology, 25(7), 851–859.
  • Naz S, Nawab K, Bano N, Rafique S, Ali U, Khubaib M, Ali U, Ismaila U, Rehman U, Tariq A, Ali M. (2020) Comparative Study of Proximate Parameters of both Farmed and Wild Selected Fish Species. Adv. Biores., Vol 11 (5) September 2020: 21-29.





  • Bano N, Grieco J, Schmelz EM. (2026) Integrin-mediated signaling, mitobiogenesis, and therapeutic implications in ovarian cancer metastasis. Publication in progress.

  • Bano N, Schmelz EM. (2026). The interplay between extracellular matrix remodeling and integrin switching in cancer metastasis. Review manuscript in preparation.

Presentations

  • Bano, N., Lewis, I., Amin, M., Schmelz, E.M. Integrin expression switching during ovarian cancer progression. Presented at the annual AACR meeting, Chicago, IL, April 5-10, 2025


  • Bano, N., Schmelz, E.M. Integrin expression switching during ovarian cancer metastasis. Flash Talk at the 41st GPSS Graduate Research symposium Virginia Tech University, Va, Mar 26, 2025


  • Bano, N., Schmelz, E.M. Sticky molecules: The secret behind ovarian cancer spread. The Nutshell Game Flash Talk, Moss Art Center, Virginia Tech, Blacksburg, VA, Nov 02, 2024


  • Bano, N., Schmelz, E.M. How cancer cells stick to new places. Flip the Fair 2024, Melrose Branch Library Roanoke, VA, Sep 25, 2024


  • Bano, N., Schmelz, E.M. Integrin expression switching during ovarian cancer progression. Presented at the Spring ILSB poster session event, Virginia Tech, Blacksburg, VA, May 05, 2024


  • Bano, N., Schmelz, E.M. Integrin expression switching during ovarian cancer progression. Presented at the American Association for Cancer Research, San Diego, CA, April 5-10, 2024


  • Bano, N., Schmelz, E.M. Integrin expression switching during ovarian cancer progression. Presented at the 40th GPSS Graduate Research symposium Virginia Tech University, Va, Mar 27, 2024


  • Bano, N., Schmelz, E.M. Integrin expression switch during ovarian cancer progression. Presented at the Translational Biology Medicine and Health Winter Research symposium at Fralin Biomedical Research Institute, Roanoke, VA, Jan 18, 2024


  • Bano, N., Oldakowski, S, Schmelz, E.M. Integrins expression switch during ovarian cancer progression. Presented at the TBMH open house event, Virginia Tech, Roanoke, VA, October 20, 2023


  • Bano, N., Schmelz, E.M. Differences in energy metabolism between spheroids in ovarian cancer stem cells and ovarian epithelial cancer cells. Presented at the Virginia Tech Cancer Research Alliance Retreat at Children National Hospital, Washington, DC, May 25, 2023


  • Bano, N., Schmelz, E.M. Differences in energy metabolism between spheroids in ovarian cancer stem cells and ovarian epithelial cancer cells. Presented at Translational Biology Medicine and Health Winter Research symposium at Fralin Biomedical Research Institute, Roanoke VA, Jan 18, 2023
  • Virginia Tech Graduate Research Development Program Grant (2025) to support research on integrin-driven downstream signaling cascade in ovarian cancer metastasis


  • NPLB Biotech Fellowship Summer 2025, project work on looking beyond the brand (NPLB): Paclitaxel (Taxol) and the path from nature to generic medicine


  • Award in the Radical Results category at Flip the Fair 2024 poster presentation for the project, How cancer cells stick to new places, Virginia Tech University


  • Travel grant to annual AACR meeting, HNFE, 2025, Virginia Tech


  • Associate Member The Royal Society of Biology


  • Associate Member The American Association for Cancer Research and Women in Cancer Research


  • Member Sigma Xi, The Scientific Research Honor Society


  • Member The American Society of Clinical Oncology


  • Member Phi Sigma Biological Sciences Honor Society
  • Director of Communication, Pakistan Students and Professionals’ Association, Virginia Tech, 2025-Present


  • Reviewer for Graduate Research Development Program grant proposals during the Fall 2025 cycle at Virginia Tech University