## 3 Hsp60 in Carcinogenesis  
An indication of Hsp60 involvement in carcinogenesis is its altered expression and localization observed in certain human cancers [47; 49; 85]. However, the exact role of Hsp60 in cancer remains undefined and seems to change depending on the molecular and cytological context (Table 2). Hsp60 was found increased in various malignancies: cervical and ovarian [86; 87; 88; 89; 90], breast [91; 92], colorectal [93], lung [94; 95], prostate [96], gastric [97; 98], and thyroid cancers [99; 100]; and in leukemias [101], and glioblastoma multiforme [102; 103; 104]. The data in general suggest that Hsp60 is actively involved in carcinogenesis as a pro-tumorigenic factor, because its increase and location changes positively correlated with tumor development and malignancy. Moreover, in some cancers, the Hsp60 increase was also associated with a heightened resistance to anti-cancer drugs and other treatments [89; 105], and with metastas and angiogenesis [106; 107]. It has to be emphasized that the quantitative variations of Hsp60 in cancer cells, particularly its increase, may reflect the heightened need of the chaperone system by the malignant cells with their rapid and intensive metabolism and proliferation. Thus, the Hsp60 quantitative patterns observed would be the consequence of the disease but not a distinct etiological factor. We argue that even so, Hsp60 aids the tumor in what we call a chaperonopathy by mistake or collaborationism because the tumor depends on its help. What is the value of this concept? It puts Hsp60 in the stage's center and presents it as a target for developing treatment strategies aimed at inhibiting-blocking this collaborator with the enemy from the inside. For example, Hsp60 downregulation by chemical compounds suppressed cancer-cell proliferation and tumor progression and enhanced the beneficial effects of anti-cancer treatments [62; 69; 90; 108; 109; 110; 111; 112]. It was observed that Hsp60 knockdown inhibited tumor progression by altering mitochondrial homeostasis and inactivating the mTOR pathway, in ovarian cancer and glioblastoma [90; 109]. In colorectal cancer, Hsp60 inhibition promoted the tumor-suppressive activity of insulin-like growth factor binding protein 7 (IGFBP7) [108]. Treatment of a neuroblastoma cell line with curcumin caused cell death by diminishing the cellular level of Hsp60 [111]. It was suggested that this cytotoxic effect was induced through the downregulation of survivin, whose expression was shown to be positively correlated with the expression of CCAR2 and Hsp60 in neuroblastoma tissues and cell lines [113]. Thus, it is becoming clear that the positive correlation between Hsp60 overexpression and increase in cancer cell proliferation and survival depends on the interaction of the chaperonin with proteins involved in cell cycle and apoptosis. In cancer cells lines, Hsp60 played a cytoprotective and pro-survival role by stabilizing the mitochondrial level of survivin and blocking p53-mediated apoptosis [62; 113], or by inhibiting the intracellular isoform of clusterin [114]. In other cases, the pro-tumorigenic role of Hsp60 involved blocking the caspase-dependent apoptosis through the negative regulation of mitochondrial permeability transition [102], or the inhibition of pro-caspase 3 proteolytic activation [115; 116]. However, others have reported that in some types of cancer, Hsp60 was decreased, downregulated not increased or, if increased, caused tumor suppression not enhancement [117; 118]. For instance, Hsp60 was decreased in hepatocellular carcinoma (HCC) tissue compared to pertumor tissue, and this pattern positively correlated with high serum AFP (alpha-fetoprotein) level and poor overall survival. Conversely, increased Hsp60 inhibited invasion and migration of HCC cells both in vitro and in vivo, correlating with a better prognosis [118].