Mutant p53 proteins alter cancer cell secretome and tumour microenvironment: Involvement in cancer invasion and metastasis.

An ever-increasing number of studies highlight the role of mutant p53 proteins in the alteration of cancer cell secretome and in the modification of tumour microenvironment, sustaining an invasive phenotype of cancer cell. The knowledge of the molecular mechanisms underlying the interplay between mutant p53 proteins and the microenvironment is becoming fundamental for the identification of both efficient anticancer therapeutic strategies and novel serum biomarkers. In this review, we summarize the novel findings concerning the regulation of secreted molecules by cancer cells bearing mutant TP53 gene. In particular, we highlight data from available literature, suggesting that mutant p53 proteins are able to (i) alter the secretion of enzymes involved in the modulation of extracellular matrix components; (ii) alter the secretion of inflammatory cytokines; (iii) increase the extracellular acidification; and (iv) regulate the crosstalk between cancer and stromal cells.

Cordani M ，Pacchiana R ，Butera G ，D'Orazi G ，Scarpa A ，Donadelli M ... -  《-》

p53's Extended Reach: The Mutant p53 Secretome.

Pavlakis E ，Stiewe T 《Biomolecules》

Autocrine mechanisms of cancer chemoresistance.

An ever-increasing number of studies highlight the role of cancer secretome in the modification of tumour microenvironment and in the acquisition of cancer cell resistance to therapeutic drugs. The knowledge of the mechanisms underlying the relationship between cancer cell-secreted factors and chemoresistance is becoming fundamental for the identification of novel anticancer therapeutic strategies overcoming drug resistance and novel prognostic secreted biomarkers. In this review, we summarize the novel findings concerning the regulation of secreted molecules by cancer cells compromising drug sensitivity. In particular, we highlight data from available literature describing the involvement of cancer cell-secreted molecules determining chemoresistance in an autocrine manner, including: i) growth factors; ii) glycoproteins; iii) inflammatory cytokines; iv) enzymes and chaperones; and v) tumor-derived exosomes.

Butera G ，Pacchiana R ，Donadelli M 《-》

Interleukin-6 increases matrix metalloproteinase-14 (MMP-14) levels via down-regulation of p53 to drive cancer progression.

Cathcart JM ，Banach A ，Liu A ，Chen J ，Goligorsky M ，Cao J ... -  《Oncotarget》

Extracellular Vesicles: Messengers of p53 in Tumor-Stroma Communication and Cancer Metastasis.

Pavlakis E ，Neumann M ，Stiewe T 《INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES》