TY - JOUR
T1 - A Proteomic Connectivity Map for Characterizing the Tumor Adaptive Response to Small Molecule Chemical Perturbagens
AU - Zi, Zhenzhen
AU - Zhang, Yajie
AU - Zhang, Peng
AU - Ding, Qing
AU - Chu, Michael
AU - Chen, Yiwen
AU - Minna, John D.
AU - Yu, Yonghao
N1 - Funding Information:
This work was supported in part by grants from the Welch Foundation (I-1800 to Y.Y.), NIH (R01GM122932 and R01GM114160 to Y.Y., P50CA070907 to J.D.M., and R01GM130838 to Y.C.), American Cancer Society (RSG-15-062-01-TBE to Y.Y.), Bristol-Myers Squibb-MRA Young Investigator Award in Immunotherapy (#569414 to Y.C.), and CPRIT (RP160157 to Z.Z. and RP160652 to J.D.M.).
Funding Information:
The authors declare the following competing financial interest(s): Y.Y. receives research support from Pfizer. Acknowledgments
Publisher Copyright:
Copyright © 2019 American Chemical Society.
PY - 2020/1/17
Y1 - 2020/1/17
N2 - A powerful means to understand the cellular function of corrupt oncogenic signaling programs requires perturbing the system and monitoring the downstream consequences. Here, using a unique pair of non-small cell lung cancer (NSCLC)/normal lung epithelial patient-derived cell lines (HCC4017/HBEC30KT), we systematically interrogated the remodeling of the NSCLC proteome upon treatment with 35 chemical perturbagens targeting a diverse array of mechanistic classes. HCC4017 and HBEC30KT cells differ significantly in their proteomic response to the same compound treatment. Using protein covariance analyses, we identified a large number of functional protein networks. For example, we found that a poorly studied protein, C5orf22, is a novel component of the WBP11/PQBP1 splicing complex. Depletion of C5orf22 leads to the aberrant splicing and expression of genes involved in cell growth and immunomodulation. In summary, we show that by systematically measuring the tumor adaptive responses at the proteomic level, an understanding could be generated that provides critical circuit-level biological insights for these pharmacologic perturbagens.
AB - A powerful means to understand the cellular function of corrupt oncogenic signaling programs requires perturbing the system and monitoring the downstream consequences. Here, using a unique pair of non-small cell lung cancer (NSCLC)/normal lung epithelial patient-derived cell lines (HCC4017/HBEC30KT), we systematically interrogated the remodeling of the NSCLC proteome upon treatment with 35 chemical perturbagens targeting a diverse array of mechanistic classes. HCC4017 and HBEC30KT cells differ significantly in their proteomic response to the same compound treatment. Using protein covariance analyses, we identified a large number of functional protein networks. For example, we found that a poorly studied protein, C5orf22, is a novel component of the WBP11/PQBP1 splicing complex. Depletion of C5orf22 leads to the aberrant splicing and expression of genes involved in cell growth and immunomodulation. In summary, we show that by systematically measuring the tumor adaptive responses at the proteomic level, an understanding could be generated that provides critical circuit-level biological insights for these pharmacologic perturbagens.
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U2 - 10.1021/acschembio.9b00694
DO - 10.1021/acschembio.9b00694
M3 - Article
C2 - 31846293
AN - SCOPUS:85078506200
SN - 1554-8929
VL - 15
SP - 140
EP - 150
JO - ACS Chemical Biology
JF - ACS Chemical Biology
IS - 1
ER -