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Khaket, Tejinder Pal,Singh, Mahendra Pal,Khan, Imran,Bhardwaj, Monika,Kang, Sun Chul Elsevier 2018 Cellular signalling Vol.46 No.-
<P><B>Abstract</B></P> <P>As Autophagy is a pivotal mechanism of cancer cell survival and the development of chemotherapeutic resistance; therefore, new approaches are warranted for its targeting which may be fulfilled by cathepsins regulation. Amongst cathepsins, cathepsin C (CTSC) is highly expressed in various cancers and possesses significant therapeutic potential in autoimmune disorders; however, its role in colorectal cancer has not been explored. Herein, we aimed to investigate the role of CTSC in autophagy regulation mediated colorectal carcinoma cell proliferation. Cathepsin C targeting through inhibitors/siRNA leads to the accumulation of light chain 3 II and p62 without affecting the lysosomal integrity, revealed dysfunctional autolysosomal degradation which is also substantiated by proteolytic studies. Cathepsin C inhibition showed comparable autophagy blockade with E64d and augmented the autophagy blockade mediated by bafilomycin. Loss of CTSC function also induced ER stress-mediated JNK phosphorylation accompanied by the translocation of mitochondrial cyt <I>c</I> followed by apoptotic cell death in colorectal carcinoma cells. Taken together, the study reveals that CTSC targeting plays a key role in the regulation of autophagy mediated colorectal cancer cell proliferation. Further investigations are required to determine the functional role of CTSC in other tumors also which may have implications for the therapeutic prevention of cancer in the future.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Cathepsin C targeting leads to the accumulation of autophagolysosomes which supported the key role of cathepsin C activity in autophagy regulation. </LI> <LI> Cathepsin C inhibition augmented the autophagy blockade caused by bafilomycin. </LI> <LI> In colorectal cancer cells, cathepsin C inhibition induced ER-stress and JNK signaling mediated apoptosis in HCT-116 cells. </LI> <LI> GFDMK treated cells enhances the sensitivity of colorectal cells toward E64d. </LI> </UL> </P>
Breast cancer metastasis: Putative therapeutic role of vascular cell adhesion molecule-1
Sharma, R.,Sharma, R.,Khaket, T. P.,Dutta, C.,Chakraborty, B.,Mukherjee, T. K. Springer Science + Business Media 2017 CELLULAR ONCOLOGY Vol.40 No.3
<P>Conclusions This study focuses on recent progress on the role of VCAM-1, an important glycoprotein belonging to the immunoglobulin (Ig) superfamily of cell surface adhesion molecules in breast cancer angiogenesis, survival and metastasis. Targeting VCAM-1, expressed on the surface of breast cancer cells, and/or its specific ligand VLA-4/alpha 4 beta 1 integrin, expressed on cells at the site of metastasis, may be a useful strategy to reduce breast cancer cell invasion and metastasis. Various approaches to therapeutically target VCAM-1 and VLA-4 are also discussed.</P>