title: Angiogenic growth factor axis in autophagy regulation.
abstract: Understanding the molecular mechanisms promoting therapy resistance is important. Previously, we reported that VEGFC can promote cancer cell survival during stress via interaction with its receptor NRP2. While examining the molecular mechanisms involved in this survival, we performed a microarray study in which we identified two genes, WDFY1 and LAMP2, which have been suggested to function in autophagy. Our subsequent studies further confirmed the regulation of autophagy by the VEGFC-NRP2 axis in cancer during starvation- and chemotherapy-induced stress. We are currently in the process of determining the mechanism(s) through which WDFY1 and LAMP2 control autophagy; however, we did observe an increase in MTOR complex 1 (MTORC1) activity after the depletion of the VEGFC-NRP2 axis. It would therefore be interesting to study whether WDFY1 and LAMP2 can influence MTORC1 activity and regulate autophagy. Taken together, our data suggest that targeting the VEGFC-NRP2 axis in combination with chemotherapy could be an effective treatment for advanced cancers.
authors: Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.
authors: Marissa J
authors: MJ
authors: Stanton
authors: Samikshan
authors: S
authors: Dutta
authors: Navatha Shree
authors: NS
authors: Polavaram
authors: Sohini
authors: S
authors: Roy
authors: Michael H
authors: MH
authors: Muders
authors: Kaustubh
authors: K
authors: Datta
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000378:metabolism*; D001343:Autophagy; D045744:Cell Line, Tumor; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D039943:Neuropilin-2 / Q000378:metabolism; D010588:Phagosomes / Q000378:metabolism; D015398:Signal Transduction; D042582:Vascular Endothelial Growth Factor C / Q000378:metabolism
chemical_list: D043925:Angiogenesis Inducing Agents; D039943:Neuropilin-2; D042582:Vascular Endothelial Growth Factor C
keywords: LAMP-2; NRP-2; VEGF-C; WDFY1; autophagy; chemotherapy