» Articles » PMID: 20164124

Secreted Protein Acidic and Rich in Cysteine-induced Cellular Senescence in Colorectal Cancers in Response to Irinotecan is Mediated by P53

Overview
Journal Carcinogenesis
Specialty Oncology
Date 2010 Feb 19
PMID 20164124
Citations 8
Authors
Affiliations
Soon will be listed here.
Abstract

Cellular senescence is another mechanism that can be exploited to achieve better chemosensitivity and greater tumor regression. Unlike apoptosis, cellular senescence can be induced at much lower concentrations of chemotherapy that are better tolerated by patients. We previously revealed that secreted protein acidic and rich in cysteine (SPARC), a matricellular protein, may function as a modulator of chemotherapy sensitivity by enhancing apoptosis. Here, we examine the effects of SPARC on cellular senescence in the presence of chemotherapy. Cellular senescence is induced only in sensitive colorectal cancer (CRC) cells with low concentrations of irinotecan (CPT-11). However, CPT-11-resistant cells exposed to endogenous or exogenous SPARC can also be triggered into cellular senescence. This induction is associated with higher levels of p16(INK4A) and phosphorylated p53. Knock down of p16(INK4A) reduces drug-induced senescence in all cells, but knock down and overexpression of p53 modulates senescence only in cells exposed to SPARC. Furthermore, treatment of mice with SPARC and CPT-11 leads to significantly increased cellular senescence and tumor regression. The chemosensitizing effects of SPARC in CRCs are, therefore, probably mediated in part by activating cellular senescence.

Citing Articles

Single-cell analysis of menstrual endometrial tissues defines phenotypes associated with endometriosis.

Shih A, Adelson R, Vashistha H, Khalili H, Nayyar A, Puran R BMC Med. 2022; 20(1):315.

PMID: 36104692 PMC: 9476391. DOI: 10.1186/s12916-022-02500-3.


Epstein-Barr virus miR-BART3-3p promotes tumorigenesis by regulating the senescence pathway in gastric cancer.

Wang J, Zheng X, Qin Z, Wei L, Lu Y, Peng Q J Biol Chem. 2019; 294(13):4854-4866.

PMID: 30674552 PMC: 6442059. DOI: 10.1074/jbc.RA118.006853.


Exosomes confer pro-survival signals to alter the phenotype of prostate cells in their surrounding environment.

Hosseini-Beheshti E, Choi W, Weiswald L, Kharmate G, Ghaffari M, Roshan-Moniri M Oncotarget. 2016; 7(12):14639-58.

PMID: 26840259 PMC: 4924741. DOI: 10.18632/oncotarget.7052.


Secreted protein acidic and rich in cysteine enhances the chemosensitivity of pancreatic cancer cells to gemcitabine.

Fan X, Mao Z, Ma X, Cui L, Qu J, Lv L Tumour Biol. 2015; 37(2):2267-73.

PMID: 26358255 DOI: 10.1007/s13277-015-4044-4.


Tumour-microenvironment interactions: role of tumour stroma and proteins produced by cancer-associated fibroblasts in chemotherapy response.

Hale M, Hayden J, Grabsch H Cell Oncol (Dordr). 2013; 36(2):95-112.

PMID: 23494412 DOI: 10.1007/s13402-013-0127-7.