TY - JOUR
T1 - Integrative proteomic and transcriptomic analysis provides evidence for TrkB (NTRK2) as a therapeutic target in combination with tyrosine kinase inhibitors for non-small cell lung cancer
AU - Gomez, Daniel Richard
AU - Byers, Lauren Averett
AU - Nilsson, Monique
AU - Diao, Lixia
AU - Wang, Jing
AU - Li, Lerong
AU - Tong, Pan
AU - Hofstad, Mia
AU - Saigal, Babita
AU - Wistuba, Ignacio
AU - Kalhor, Neda
AU - Swisher, Stephen
AU - Fan, Youhong
AU - Hong, Waun Ki
AU - Suraokar, Milind
AU - Behrens, Carmen
AU - Moran, Cesar
AU - Heymach, John Victor
N1 - Publisher Copyright:
© Gomez et al.
PY - 2018
Y1 - 2018
N2 - While several molecular targets have been identified for adenocarcinoma (ACA) of the lung, similar drivers with squamous cell carcinoma (SCC) are sparse. We compared signaling pathways and potential therapeutic targets in lung SCC and ACA tumors using reverse phase proteomic arrays (RPPA) from two independent cohorts of resected early stage NSCLC patients: a testing set using an MDACC cohort (N=140) and a validation set using the Cancer Genome Atlas (TCGA) cohorts. We identified multiple potentially targetable proteins upregulated in SCC, including NRF2, Keap1, PARP, TrkB, and Chk2. Of these potential targets, we found that TrkB also had significant increases in gene expression in SCC as compared to adenocarcinoma. Thus, we next validated the upregulation of TrkB both in vitro and in vivo and found that it was constitutively expressed at high levels in a subset of SCC cell lines. Furthermore, we found that TrkB inhibition suppressed tumor growth, invasiveness and sensitized SCC cells to tyrosine kinase EGFR inhibition in a cell-specific manner.
AB - While several molecular targets have been identified for adenocarcinoma (ACA) of the lung, similar drivers with squamous cell carcinoma (SCC) are sparse. We compared signaling pathways and potential therapeutic targets in lung SCC and ACA tumors using reverse phase proteomic arrays (RPPA) from two independent cohorts of resected early stage NSCLC patients: a testing set using an MDACC cohort (N=140) and a validation set using the Cancer Genome Atlas (TCGA) cohorts. We identified multiple potentially targetable proteins upregulated in SCC, including NRF2, Keap1, PARP, TrkB, and Chk2. Of these potential targets, we found that TrkB also had significant increases in gene expression in SCC as compared to adenocarcinoma. Thus, we next validated the upregulation of TrkB both in vitro and in vivo and found that it was constitutively expressed at high levels in a subset of SCC cell lines. Furthermore, we found that TrkB inhibition suppressed tumor growth, invasiveness and sensitized SCC cells to tyrosine kinase EGFR inhibition in a cell-specific manner.
KW - Lung cancer
KW - Proteomics
KW - Squamous cell carcinoma
KW - TrkB
UR - http://www.scopus.com/inward/record.url?scp=85042930977&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85042930977&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.24361
DO - 10.18632/oncotarget.24361
M3 - Article
C2 - 29581842
AN - SCOPUS:85042930977
SN - 1949-2553
VL - 9
SP - 14268
EP - 14284
JO - Oncotarget
JF - Oncotarget
IS - 18
ER -