## 3 Hsp60 in Carcinogenesis
All the above observations (Table 2) make clear that Hsp60 has different roles in carcinogenesis that deserve investigation to elucidate the molecular mechanisms involved, particularly those determining whether the chaperonin acts against or for the cancer cell. Some data in the literature support the assumption that Hsp60 acts as a pro-tumor protein, considering its role in the modulation of anti-apoptotic factors. It is known that during tumorigenesis, cells undergo complex transcriptional events that lead to a dysregulation of numerous factors. In this scenario, transformed cells show the typical phenotype of the proteotoxic stress, in which the consequent Hsp60 overexpression is a key event because of its central role in the regulation of protein homeostasis. Conversely, the observation that, in several types of tumors, such as lung cancer, Hsp60 levels are reduced, further demonstrate that its functioning is not only related to protein folding and the maintenance of protein homeostasis, but is complex and dependent on the cell and tissue type, its molecular interactors and its localization inside or outside the mitochondria and the cell. Thus, the multifaceted and at times contradictory functions of Hsp60 in cancer are still poorly understood and deserve active investigation, considering the importance of the chaperonin for survival of cells, normal or malignant. \begin{table}
\begin{tabular}{c c c c} \hline \hline
**Cancer** & **Hsp60 Level, Location and/or Status** & **Effect** & **Reference** \\ \hline \multirow{8}{*}{Lung carcinoma} & Presence of Hsp60 on cancer-cell & \multirow{4}{*}{Possible involvement in cell-to-cell} \\  & plasma-cell membrane and on & & communication and anti-tumor immune \\  & membrane of cancer cell-derived & & response stimulation \\  & exosomes & & \\ \cline{2-4}  & Decrease of intracellular Hsp60 level & Hsp60/p53 complex dissociation and & \\  & and increase of Hsp60 acetylation level & restoration of cancer-cells replicative & [69] \\  & after doxorubicin treatment & senescence & \\ \cline{2-4}  & Decrease of intracellular Hsp60 level & Dissociation of the Hsp60/pro-Caspase-3 & \\  & after CubipyOXA treatment & complex and cancer-cell apoptosis & [116] \\ \cline{2-4}  & & Increased Hsp60 level & Positive correlation with cancer progression & \\  & & and poor prognosis & [94; 96] \\ \hline \multirow{2}{*}{Otal cancer} & \multirow{2}{*}{Presence of Hsp60 on cell surface} & Interaction with gamma-delta T cells and & \\  & & transduction of anti-cancer immune response & [52] \\ \hline \multirow{2}{*}{Osteosarcoma} & Hyperacetylation and loss of & \multirow{2}{*}{Decreased viability and augmented cancer-cell} & \multirow{2}{*}{[68]} \\  & mitochondrial Hsp60 after & & death & \\  & Geldanamycin treatment & & \\ \hline \multirow{4}{*}{Breast cancer} & Increase of phosphorylated surface & \multirow{2}{*}{\(\alpha\)3\(\beta\)1 integrin activation and enhancement of \multirow{2}{*}{[70]}} & \multirow{2}{*}{[70]} \\  & Hsp60 & cancer cells motility and adhesion & \\ \cline{2-4}  & & Enhanced cancer-cell proliferation and reduced & \\ \cline{1-1} \cline{2-4}  & Increased cytosolic Hsp60 & apoptosis; positive correlation with worse & \\ \cline{1-1} \cline{2-4}  & & disease-free survival and poor prognosis & \\ \hline \multirow{2}{*}{Bronchial carcinoma} & Decreased Hsp60 level & Positive correlation with bronchial cancer & \\  & & development and progression & \\ \hline \multirow{2}{*}{Cervical cancer} & Increased Hsp60 level & Positive correlation with cancer progression & [86; 87; 88; 89; 90; 91; 92; 93; 94; 95; 96; 97; 98; 99; 100; 99; 100; 99; 100; 99; 101; 102; 103; 104; 105; 106; 107; 108; 109; 100; 101; 102; 104; 106; 107; 109; 100; 103; 108; 109; 100; 104; 107; 109