Ribosomal protein S3 regulates XIAP expression independently of the NF-κB pathway in breast cancer cells

Abstract

The X-linked inhibitor of apoptosis (XIAP) confers the resistance of various types of cancer to standard chemotherapeutic agents such as anthracycline and taxane. In breast cancer, XIAP is known to be overexpressed. However, the mechanisms underlying the overexpression of XIAP remain currently unclear. In order to elucidate the mechanisms responsible for the overexpression of the XIAP protein in breast cancer, we attempted to clarify the mechanisms by which the natural compound curcumin downregulates XIAP in breast cancer cells. In that process, we identified the ribosomal protein S3 (RPS3) as a curcumin‑binding protein using curcumin-fixed magnetic FG beads. The knockdown of RPS3 inhibited cell growth and induced apoptosis as well as the downregulation of XIAP in breast cancer cells. Although RPS3 is known to directly bind to and activate the nuclear factor-κB (NF-κB), which induces several anti-apoptotic genes such as XIAP, the knockdown of RPS3 unexpectedly reduced the levels of the XIAP protein, but not the mRNA level of XIAP and the transcription factor NF-κB activity. These results reveal that RPS3 upregulates XIAP independently of the NF-κB pathway in human breast cancer cells.

The histone deacetylase inhibitor OBP-801 and eribulin synergistically inhibit the growth of triple-negative breast cancer cells with the suppression of survivin, Bcl-xL, and the MAPK pathway

“…Cell growth was evaluated using the Cell Counting Kit-8 (CCK-8) (Dojindo, Kumamoto, Japan), as previously reported [13].…”

“…When nuclear extracts were prepared from the cells treated with agents, Nuclear Extract Kit was used (Active Motif, Carlsbad, CA). Western blotting was performed, as previously reported [13]. Primary antibodies were rabbit anti …”

“…Total cellular RNA extraction from SUM159PT and MDA-MB-231 cells and complementary DNA (cDNA) synthesis were performed as previously reported [13]. A quantitative real-time RT-PCR analysis was performed with the cDNA and TaqMan probes (Thermo Fisher Scientific, Waltham, MA) to survivin (Hs04194392_s1) and GAPDH (Hs02758991_g1).…”

Ribosomal protein S27-like regulates autophagy via the β-TrCP-DEPTOR-mTORC1 axis

“…It has been documented that ribosomal proteins play important roles in the genesis and progression of breast cancer, one of the most common cancers diagnosed in women around the world 5 . For example, knockdown of RPS3 6 , RPS6 7 , and RPL24 8 in breast cancer cells inhibited cell growth, viability, or proliferation, or induced apoptosis in cell based studies. Moreover, downregulation of RPS19 or RPL39 suppressed breast tumor growth and progression in a transgenic breast cancer model, or tumor initiation and lung metastasis in patient-derived and human breast cancer xenografts, respectively 9 , 10 .…”

Chaperone-E3 Ligase Complex HSP70-CHIP Mediates Ubiquitination of Ribosomal Protein S3

“…In addition, ribosomal proteins are involved in apoptosis as follows: RPS3a is thought to participate in the apoptosis of NIH3T3 cells [ 7 ], and a knockdown of RPS3 leads to improved cell survival after H 2 O 2 treatment [ 8 ]. Moreover, in breast cancer cells, a knockdown of RPS3 induces apoptosis by downregulating X-linked inhibitor of apoptosis (XIAP) [ 9 ]. Nonetheless, RPS3 has previously been reported to induce antiapoptotic genes such as X-linked inhibitor of apoptosis by activating nuclear factor κB [ 10 ].…”