Researchers found that the autophagy – a process involving the cell degradation of the unnecessary or dysfunctional cellular components – activates the Wnt pathway but the signal transduction pathways maintaining autophagy in the developing embryo still needs work.
Researchers found that Gli1 and Gli3 are involved in autophagy regulation but the contribution still needs further research. Gli1 and Gli3 are the types of transcription factors that are involved in the flow of genetic information from the DNA to mRNA.
The role of the upstream activator, Smo, for the effects of Gli2 and Ci on autophagy is not much clear.
The role of autophagy in cancer is argumentative and complicated. Moreover, further research on the Hedgehog signaling pathway related to the increase or decrease of the progression of the tumors have to be done.
Researchers worked on cyclopamine, a naturally occurring chemical inhibiting the Hedgehog signalling pathway, and found that it acts on autophagy in two opposite ways. One way increases the autophagosome production by stopping the Smo activity while the other way disturbs the autophagosome maturation through the mechanism that is still not clear but that is dependent on Gli2. The drug has additional molecular targets than the presently known targets as shown by the effects of cyclopamine independent of Smo inhibition in human breast cancer cell lines and in zebrafish.
eIF2α controls autophagy but the exact mechanism behind this control is not much clear.
In another process, further work has to be done on LC3 and Atg5 that the transcriptional inductions of these are involved in autophagy.
Jimenez-Sanchez, M., Menzies, F., Chang, Y., Simecek, N., Neufeld, T., & Rubinsztein, D. (2012). The Hedgehog signalling pathway regulates autophagy Nature Communications, 3 DOI: 10.1038/ncomms2212