=====Cathepsin L=====
[[Cathepsin]] L is a [[lysosomal cysteine protease]] that plays important roles in cancer [[tumorigenesis]], proliferation and chemotherapy resistance. 

It is exclusively elevated in a variety of malignancies, including [[glioma]]s. 

Cathepsin L acts as an upstream regulator of [[NF-κB]] activation in human [[glioma cell]]s and contributes to their sensitivity to [[ionizing radiation]] (IR) [[in vitro]]. Inhibition of cathepsin L can sensitize the cells to IR
((Yang N, Wang P, Wang WJ, Song YZ, Liang ZQ. Inhibition of cathepsin L
sensitizes human glioma cells to ionizing radiation in vitro through NF-κB
signaling pathway. Acta Pharmacol Sin. 2015 Mar;36(3):400-10. doi:
10.1038/aps.2014.148. Epub 2015 Feb 9. PubMed PMID: 25661319; PubMed Central
PMCID: PMC4349927.
)).

Cathepsin L is involved in modulation of [[radiosensitivity]] in human glioma [[U251]] cells (harboring the mutant type [[p53]] gene) in vitro
((Zhang QQ, Wang WJ, Li J, Yang N, Chen G, Wang Z, Liang ZQ. Cathepsin L
suppression increases the radiosensitivity of human glioma U251 cells via G2/M
cell cycle arrest and DNA damage. Acta Pharmacol Sin. 2015 Sep;36(9):1113-25.
doi: 10.1038/aps.2015.36. Epub 2015 Jun 22. PubMed PMID: 26095040; PubMed Central
PMCID: PMC4561966.
)).

A [[study]] assessed whether [[knockdown]] of Cathepsin L can influence GSC growth, tumor [[radiosensitivity]], and clinical [[outcome]]. Protein levels of Cathepsin L and [[stem cell marker]]s (CD133 and Nestin) were analyzed in samples from 90 gliomas of different WHO grades and 6 normal brain tissues by [[immunohistochemistry]]. Two glioma stem cell lines with overexpressed Cathepsin L were stably transfected with Cathepsin L [[small hairpin RNA]] expression vectors. The effect of Cathepsin L inhibition on radiosensitivity, self-renewal, stemness, DNA damage, and apoptosis were evaluated. In addition, an intracranial animal model and subcutaneous tumor xenografts in nude mice were used to assess tumor response to Cathepsin L inhibition in vivo. 

The results proved that expression of Cathepsin L and CD133, but not of Nestin, correlated with malignant grades of glioma tissues. GSCs with high Cathepsin L and CD133 co-expression were extraordinarily radioresistant. Cathepsin L inhibition with radiotherapy significantly reduced GSC growth, promoted apoptosis, and improved radiosensitivity. Knockdown of Cathepsin L resulted in a dramatic reduction of CD133 expression, as well as the decreased phosphorylation of DNA repair checkpoint proteins (ATM and DNA-PKcs). Furthermore, combination of Cathepsin L inhibition and radiotherapy potently blocked tumor growth and decreased blood vessel formation in vivo. Taken together, these findings suggest the Cathepsin L as a promising therapeutic target for clinical therapy in GBM patients
((Wang W, Long L, Wang L, Tan C, Fei X, Chen L, Huang Q, Liang Z. Knockdown of
Cathepsin L promotes radiosensitivity of glioma stem cells both in vivo and in
vitro. Cancer Lett. 2015 Dec 16. pii: S0304-3835(15)00753-3. doi:
10.1016/j.canlet.2015.12.012. [Epub ahead of print] PubMed PMID: 26706414.)).