Fig 2: High level of SBDS is associated with unfavorable cancer prognosis.a, b Colorectal cancer tissue array analysis shows that SBDS is significantly overexpressed in cancer versus normal tissues. c–n The Kaplan–Meier survival analysis indicate that high expression of endogenous SBDS predicts poor patient survival in a wide spectrum of human cancers, including bladder cancer c, breast cancer d, cervical cancer e, colorectal cancer f, glioma g, head and neck cancer h, lung cancer i, ovarian cancer j, pancreatic cancer k, stomach cancer l, thymoma m, and uterine endometrial cancer n.

Fig 3: Ablation of endogenous SBDS inhibits cancer cell growth and invasion.a, b Knockdown of SBDS by siRNA inhibits proliferation of HCT116p53+/+ cells more dramatically than that of HCT116p53-/- cells. Cells were transfected with control or SBDS siRNA and re-seeded in 96-well plate followed by the cell viability assay. c, d Knockdown of SBDS by shRNAs inhibits proliferation of HCT116p53+/+ cells more dramatically than that of HCT116p53-/- cells. Cells were infected with control or SBDS-shRNA lentiviruses and re-seeded in 96-well plate followed by the cell viability assay. e, f Knockdown of SBDS induces sub-G1 accumulation of HCT116p53+/+ cells but not HCT116p53-/- cells. Cells were transfected with control or SBDS siRNA for 48–72 hr followed by flow cytometry analyses. g, h Knockdown of SBDS prevents invasion of HCT116p53+/+ cells more dramatically than that of HCT116p53-/- cells. Cells were transfected with control or SBDS siRNA followed by the transwell cell invasion assay.

Fig 4: Ablation of endogenous SBDS activates p53 pathway.a–c Knockdown of SBDS elevates the protein levels of p53 and its target genes, PUMA and p21. HCT116p53+/+ a, H460 b, and SK-MEL-147 c cell lines were transfected with control or SBDS siRNA followed by IB analyses using antibodies as indicated. d Knockdown of SBDS induces p53 accumulation in the nucleus. Cells were transfected with control or SBDS siRNA followed by IF staining assay. The white arrows indicate the nucleoli. e, f Knockdown of SBDS in HCT116p53+/+ e and H460 f cells elevates the mRNA expression of p53 target genes, including BAX, BTG2, MDM2, PUMA, and p21, by qRT-PCR analyses. g Knockdown of SBDS by lentivirus-delivered shRNAs elevates the protein expression of p53 and its target genes, MDM2 and p21. HCT116p53+/+ cells were infected with lentiviruses and harvested for IB analysis using antibodies as indicated. h Knockdown of SBDS in HCT116p53+/+ cells by lentivirus-delivered shRNAs elevates the mRNA expression of p53 target genes, including BAX, MDM2, PUMA, and p21, by qRT-PCR analyses. i Knockdown of SBDS in HCT116p53-/- cells does not affect the expression of p53 target genes at RNA levels. The same experiment was conducted using p53-deficient HCT116 cells as that done for e.

Fig 5: Ectopic SBDS suppresses tumor growth in vivo.a Ectopic SBDS does not affect body weights of the mice bearing tumors derived from HCT116p53+/+ cells. b Ectopic SBDS suppresses growth of the xenograft tumors derived from HCT116p53+/+ cells in vivo. c Representation of the dissected tumors derived from HCT116p53+/+ cells expressing the empty vector or ectopic SBDS. d, e Ectopic SBDS activates p53 pathway in tumors derived from HCT116p53+/+ cells. The tumors were homogenized and lysed for qRT-PCR d or IB analysis e. f Ectopic SBDS does not affect body weights of the mice bearing tumors derived from HCT116p53-/- cells. g Ectopic SBDS does not affect growth of the xenograft tumors derived from HCT116p53-/- cells in vivo. h Representation of the dissected tumors derived from HCT116p53-/- cells expressing the empty vector or ectopic SBDS. i, j Ectopic SBDS does not affect p53 target gene expression in tumors derived from HCT116p53-/- cells. The tumors were homogenized and lysed for qRT-PCR i or IB analysis j. k Working model of dual regulation of p53 activity by SBDS. Under the normal culture condition, SBDS mostly reside in the nucleolus and cytoplasm to conduct oncogenic function by boosting ribosome biogenesis and maintaining p53 at a low expression level (upper panel). In response to ribosomal stress, SBDS translocates to the nucleoplasm to execute a tumor-suppressive role by interacting with p53 and dissociating the MDM2–p53 complex (lower panel).