## 1 Introduction  
Cysteine cathepsins play an important role in intra- and extra-cellular protein degradation and thus function as key enzymes in various physiological processes, which is specifically true for the ubiquitously expressed endo- and exo-peptidase cathepsin B [1, 2, 3, 4, 5]. Cathepsin B belongs to the cysteine peptidases, and is classically regarded as a typical endo-lysosomal enzyme, although its expression and localization are often altered, particularly in tumor cells. Therefore, it has been linked to tumor cell invasion and metastasis [6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18]. In normal human cells, cathepsin B mRNA encodes a 47-kDa polypeptide chain which consists of a prepeptide, the signal peptide, a propeptide, and a mature polypeptide chain that can be processed to yield proteolytically active single- and two-chain forms, depending on the removal of an internal propeptide between the light and heavy chains of cathepsin B. The signal peptide targets the protein for entry into the lumen of the rough endoplasmic reticulum (rER), from where it is transported to the Golgi, eventually reaching its final destination, the endo-lysosomes [4; 19]. The human cathepsin B gene is comprised of 12 exons, and in tumor cells a number of different mRNA variants may be generated by alternative splicing [20]. A splice variant has been detected that lacks exons 2 and 3, which encodes a protein lacking the 17 amino acid signal peptide and the first 34 amino acids of the propeptide. This N-terminally truncated cathepsin B form is not sorted like the regular preproenzyme via the ER and the Golgi apparatus to endo-lysosome [21; 22; 23]. Rather, the N-terminally truncated specific form of cathepsin B was detected in the nucleus and may be imported into the mitochondrial matrix. Such different and unusual sub-cellular locations of cysteine cathepsin have been reported in various types of cancer tissue such as breast carcinoma, colon carcinoma, thyroid carcinoma, and melanoma [5; 8; 9; 21; 24; 25; 26; 27]. Furthermore, over-expression of N-terminally truncated cathepsin B that is destined to mitochondria can result in the initiation of cell death pathways [25; 28]. N-terminally truncated forms have also been reported for other cathepsins, such as cathepsin H in human prostate cancer cells [29], cathepsin L in embryonic fibroblasts [30], or breast carcinoma cells [31], and in cathepsin L2/V in thyroid epithelial cells [32]. Thus, according to present information available, most of the N-terminally truncated forms of cysteine cathepsin are associated with pathological conditions, more evidently with cancer [8; 12; 16; 17; 18; 32; 33; 34].  
In the present study, we investigated the localization of cathepsin B in adenocarcinoma tissue in comparison to adjacent normal colon, demonstrating altered subcellular localization. Hence, further investigations were carried out on the trafficking pathway of full-length human cathepsin B in comparison to that of an N-terminally truncated form of the same protease in the colorectal (CRC) adenocarcinoma-derived in vitro cellular model HCT116. Additionally, we studied the possible effect of cathepsin B on cell cycle progression of HCT116 cells, because we had recently observed that a related enzyme, cathepsin L, promotes G1-S phase transition in CRC cells [35]. The results indicate that the 40-kDa of cathepsin B detected in HCT116 cells is likely to be sorted to peri-nuclear aggresomes. In addition, the data suggest that mis-sorting of cathepsin B forms to the nucleus of CRC cells has no obvious proteolytic function on cell cycle progression.