1. Angiogenic growth factor axis in autophagy regulation
- Author
-
Marissa J. Stanton, Samikshan Dutta, Sohini Roy, Michael H. Muders, Navatha Shree Polavaram, and Kaustubh Datta
- Subjects
Programmed cell death ,autophagy ,Vascular Endothelial Growth Factor C ,VEGF-C ,mTORC1 ,Biology ,chemotherapy ,03 medical and health sciences ,0302 clinical medicine ,Cell Line, Tumor ,Neoplasms ,Phagosomes ,medicine ,NRP-2 ,Humans ,Molecular Biology ,030304 developmental biology ,0303 health sciences ,LAMP2 ,Mechanism (biology) ,Autophagy ,Cancer ,Cell Biology ,medicine.disease ,Autophagic Punctum ,3. Good health ,Cell biology ,Neuropilin-2 ,WDFY1 ,030220 oncology & carcinogenesis ,Cancer cell ,LAMP-2 ,Angiogenesis Inducing Agents ,Signal transduction ,Signal Transduction - 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.
- Published
- 2013