Osteoclasts (OCs) are the multinucleated, bone-resorbing giant cells originally differentiated from a monocyte/macrophage lineage. OC differentiation and maturation, also called osteoclastogenesis, are strictly regulated by a variety of signaling pathways primarily induced by the interactions of two prerequisite cytokines, macrophage colony-stimulating factor (M-CSF) and the receptor activator of nuclear factor-κB ligand (RANKL) to their respective surface receptors, c-fms and RANK, in OC precursors (pre-OCs). Rab11 has emerged as the spatiotemporal regulators of intracellular vesicular transport in the endosomal recycling system; however, how it regulates osteoclastogenesis is incompletely understood. OC-triggered bone resorption is best characterized to be immensely dependent upon lysosomal function, the intracellular acidic organelles containing more than 50 acid hydrolases secreted into bone matrix microenvironment (BME). On the contrary, it is little known about the lysosomal function on modulating the turnover of c-fms and RANK surface receptors via Rab GTPase-mediated vesicular transport, thereby dictating osteoclastogenesis. In this review, I briefly describe the mechanism underlying lysosome-induced osteoclastogenesis via the Rab11-mediated modulation of the surface receptors in OCs.

Cell division control 37 (CDC37) increases the stability of HSP90 client proteins and is thus essential for numerous intracellular oncogenic signaling pathways, playing a key role in prostate oncogenesis. Notably, elevated expression of CDC37 was found in prostate cancer cells, although the regulatory mechanisms through which CDC37 expression becomes increased are unknown. Here we show both positive and negative regulation of CDC37 gene transcription by two members of the SCAN transcription factor family- MZF1 and SCAND1, respectively. Consensus DNA-binding motifs for myeloid zinc finger 1 (MZF1 / ZSCAN6) were abundant in the CDC37 promoter region. MZF1 became bound to these regulatory sites and trans-activated the CDC37 gene whereas MZF1 depletion decreased CDC37 transcription and reduced tumorigenesis of prostate cancer cells. On the other hand, SCAND1, a zinc-fingerless SCAN box protein that potentially inhibits MZF1, accumulated at MZF1-binding sites in CDC37 gene, negatively regulated CDC37 gene and inhibited tumorigenesis. SCAND1 was abundantly expressed in normal prostate cells but was reduced in prostate cancer cells, suggesting a potential tumor suppressor role of SCAND1 in prostate cancer. These findings indicate that CDC37, a crucial protein in prostate cancer progression, is regulated reciprocally by MZF1 and SCAND1.