Finnish Cancer Center FICAN webinar: Losing adhesions to promote prostate cancer

Welcome to the next FICAN webinar. This time the webinar is organized by FICAN North. The seminar will be held online (Microsoft Teams) and is open to everyone interested in cancer research.

Speaker: Aki Manninen, Professor of Cell Biology, Leader of the Disease Networks Research Unit, Faculty of Biochemistry and Molecular Medicine, University of Oulu
Title: Losing adhesions to promote prostate cancer.

Abstract: 
Prostate cancer (PCa) is a highly heterogeneous disease with a significant hereditary risk omponent, affecting millions of men and their families worldwide. While PCa is typically slow growing, some cases are aggressive, making early identification crucial. With no cure available for metastatic PCa, early detection of the aggressive forms is critical. To aid early detection, a deeper understanding of the genetic risk factors and the early steps of tumorigenesis are needed. 

The extracellular matrix (ECM) undergoes significant remodeling during prostate cancer (PCa) progression. Cell-ECM interactions, primarily mediated by integrins, play a critical role in regulating cell growth and polarity. We have investigated the functional roles of specific integrins in PCa revealing that the disruption of coordinated focal and hemidesmosomal adhesions contributes to tumorigenic properties of PCa cells. To allow detailed investigation of the dynamics of these events during early PCa tumorigenesis, we have been developing primary prostate organoid models that better mimic the human PCa in vitro.

In my presentation, I will discuss our key findings on integrin-mediated adhesions and how their functions are linked to PCa tumorigenesis. These analyses range from altered signaling cascades to mechanical molecular connections from adhesions into the nucleus to regulate transcriptomic programs. I will also present some data from PCa organoid model.

Relevant references for this talk: 
- Cruz SP, Q. Zhang Q, Devarajan R, Paia C, Luo B, Zhang K, Koivusalo S, Qin L, Xia J, Ahtikoski A, Vaarala M, Wenta T, Wei GH, Manninen A (2024) Dampened Regulatory Circuitry of TEAD1/ITGA1/ITGA2 Promotes TGFβ1 Signaling to
Orchestrate Prostate Cancer Progression. Adv. Sci., 2305547.
- Wenta T, Schmidt A, Zhang Q, Devarajan R, Singh P, Yang X, Ahtikoski A, Vaarala M, Wei GH, Manninen A (2022) Disassembly of α6β4-mediated hemidesmosomal adhesions promotes tumorigenesis in PTEN-negative prostate cancer by targeting plectin to focal adhesions. Oncogene. 41:3804-3820.
- Devarajan R, Hawash A, Koivusalo S, Tervasmäki A, Mattila T, Zhang Q, Näpänkangas J, Ahtikoski A, Vaarala M, Pylkäs K, Izzi V, Wei GH, Manninen A (2023) Patient-derived prostate cancer organoids require α6-integrins for selfrenewal and recapitulate genetic heterogeneity and histopathology of the original tumors. Preprint Research Square: doi.org/10.21203/rs.3.rs-3209780/v1 .