The recognition of molecular mechanisms involved in cancer cell resistance to anticancer drugs may improve basic knowledge of signalling pathways and also improve outcomes in patients with drug-resistant cancers that have poor prognosis, such as triple negative breast cancer (TNBC) and metastatic melanoma. Integrins are cell surface molecules that mediate sensitivity to anticancer drugs, migration and invasion, and therefore represent a suitable target for therapy. The focal adhesions (FA) are sites of attachment between cells and extracellular matrix which, by variation of FA protein composition, may mediate differential responses upon anticancer drug exposure.
Our project investigates the molecular mechanism of sensitisation of TNBC and melanoma cell lines to anticancer drugs paclitaxel, vincristine and cisplatin upon knockdown of integrins αvβ3, αvβ5, αvβ6, α3β1, α4β1 and α5β1 using integrin subunit specific siRNAs (β3, β5, β6, αv, α3, α4 or α5). In addition, our goal is to identify how a specific integrin knockdown influences cell migration and invasion. The FA protein composition will be investigated before and upon integrin silencing. Finally, we will also monitor formation and temporal evolution of FA in living cells during spreading or migration.
The understanding of integrin pathways involved in the sensitivity to anticancer drugs, migration and invasion processes may provide novel insights into biology of these cancer cells and identify new target molecules in TNBC or melanoma.
Maja Osmak, PhD
Anamaria Brozovic, PhD
Mario Cindrić, PhD
Mirela Baus Lončar, PhD
Sanjica Rak, PhD
Nikolina Stojanović, PhD
Tihana De Zan, mag. biol. mol.
Ivana Steiner, mag. mol. biotech.
Prof. Igor Weber, PhD
Laboratory for electronic mycroscopy, Ruđer Bošković Institute, Zagreb, Croatia
Prof. Gerhard Fritz
Institute for Toxicology, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
Maja T Tomicic, PhD
Department of Toxicology, University Medical Center Mainz, Mainz, Germany