CTSD and bone cancer: We identified the lysosomal and secreted aspartate protease CTSD and focused on studying its role in CRC development, since it was reported that CTSD is expressed in a wide variety of tumor types including breast cancer [22–28], prostate cancer [29], gastric cancer [30], osteosarcoma pulmonary metastases, bone cancer [31], ovarian cancer [32] and in liver metastases of colon adenocarcinoma [33–35].