American Association for Cancer Research
Browse

Figures S1-S7 from Basal-A Triple-Negative Breast Cancer Cells Selectively Rely on RNA Splicing for Survival

Download (23.35 MB)
figure
posted on 2023-04-03, 15:02 authored by Stefanie Chan, Praveen Sridhar, Rory Kirchner, Ying Jie Lock, Zach Herbert, Silvia Buonamici, Peter Smith, Judy Lieberman, Fabio Petrocca

Figure S1: Core RNA splicing genes are frequently up-regulated in basal-like TNBC; Figure S2: PRPF8 and PRPF38A knockdown have similar effect based on gene expression; Figure S3: PRPF8 knockdown promotes G2/M arrest and histone-H3 phosphorylation in MB468 cells ;Figure S4: Ribosomal, immune response, cell cycle, mitosis and proteasome transcripts are commonly sensitive to PRPF8 knockdown across different cell lines. ;Figure S5: PRPF8 knockdown disrupts MCL1 splicing across different cell lines. ;Figure S6: MB468 and HCC1187 cells are sensitive to siRNA-mediated SF3B1 knockdown; Figure S7: E7107 suppresses HCC1187 xenograft growth at a well-tolerated dose

Funding

NCI

Boston University/Boston Medical Center Startup Fund

Breast Cancer Alliance Exceptional Project Grant

History

ARTICLE ABSTRACT

Prognosis of triple-negative breast cancer (TNBC) remains poor. To identify shared and selective vulnerabilities of basal-like TNBC, the most common TNBC subtype, a directed siRNA lethality screen was performed in 7 human breast cancer cell lines, focusing on 154 previously identified dependency genes of 1 TNBC line. Thirty common dependency genes were identified, including multiple proteasome and RNA splicing genes, especially those associated with the U4/U6.U5 tri-snRNP complex (e.g., PRPF8, PRPF38A). PRPF8 or PRPF38A knockdown or the splicing modulator E7107 led to widespread intronic retention and altered splicing of transcripts involved in multiple basal-like TNBC dependencies, including protein homeostasis, mitosis, and apoptosis. E7107 treatment suppressed the growth of basal-A TNBC cell line and patient-derived basal-like TNBC xenografts at a well-tolerated dose. The antitumor response was enhanced by adding the proteasome inhibitor bortezomib. Thus, inhibiting both splicing and the proteasome might be an effective approach for treating basal-like TNBC. Mol Cancer Ther; 16(12); 2849–61. ©2017 AACR.

Usage metrics

    Molecular Cancer Therapeutics

    Licence

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC