Cathepsin B trafficking in thyroid carcinoma cells

Area of Science:

• Biochemistry
• Cell Biology
• Oncology

Background:

• Cathepsin B is a cysteine peptidase vital for thyroid hormone processing.
• Aberrant cathepsin B localization in thyroid cancer suggests a role in invasiveness and metastasis.
• Extracellular matrix degradation by cathepsin B may drive tumor spread.

Purpose of the Study:

• To investigate cathepsin B transport in normal and cancerous thyroid cells.
• To determine if protease activity influences cathepsin B trafficking.
• To link protease localization to thyroid cancer progression.

Main Methods:

• Immunolocalization of endogenous cathepsin B and protease activity probing.
• Analysis of cathepsin B-eGFP and active-site mutant cathepsin B-C29A-eGFP transport.
• Comparison of protein trafficking in normal and three thyroid carcinoma cell lines.

Main Results:

• Both active and inactive cathepsin B chimeras reached endo-lysosomal compartments in normal cells.
• GFP-tagged cathepsin B trafficked correctly to ER, Golgi, and endo-lysosomes in cancer cells.
• Active-site mutated cathepsin B was retained in ER/Golgi, particularly in less polarized carcinoma cells, indicating transport defects.
• Thyroid carcinoma cells exhibited prominent, non-directed secretion of cathepsin B and other cysteine peptidases.

Conclusions:

• Sub-cellular localization of proteolysis is critical for tissue homeostasis.
• Altered protease trafficking in thyroid cancer cells mirrors in vivo patterns.
• Interference with protease trafficking contributes to thyroid cancer onset and progression.