Table S1 from PDK1 Signaling Toward PLK1–MYC Activation Confers Oncogenic Transformation, Tumor-Initiating Cell Activation, and Resistance to mTOR-Targeted Therapy
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posted on 2023-04-03, 20:46 authored by Jing Tan, Zhimei Li, Puay Leng Lee, Peiyong Guan, Mei Yee Aau, Shuet Theng Lee, Min Feng, Cheryl Zihui Lim, Eric Yong Jing Lee, Zhen Ning Wee, Yaw Chyn Lim, R.K. Murthy Karuturi, Qiang YuTable S1 - XLS file 316K, Supplementary table 1 shows the expression profiles of PDK1-regulated genes in HEK-Vector, -PDK1, -Myc and -E545K cells
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ARTICLE ABSTRACT
Although 3-phosphoinositide–dependent protein kinase-1 (PDK1) has been predominately linked to the phosphoinositide 3-kinase (PI3K)–AKT pathway, it may also evoke additional signaling outputs to promote tumorigenesis. Here, we report that PDK1 directly induces phosphorylation of Polo-like kinase 1 (PLK1), which in turn induces MYC phosphorylation and protein accumulation. We show that PDK1–PLK1–MYC signaling is critical for cancer cell growth and survival, and small-molecule inhibition of PDK1/PLK1 provides an effective approach for therapeutic targeting of MYC dependency. Intriguingly, PDK1–PLK1–MYC signaling induces an embryonic stem cell–like gene signature associated with aggressive tumor behaviors and is a robust signaling axis driving cancer stem cell (CSC) self-renewal. Finally, we show that a PLK1 inhibitor synergizes with an mTOR inhibitor to induce synergistic antitumor effects in colorectal cancer by antagonizing compensatory MYC induction. These findings identify a novel pathway in human cancer and CSC activation and provide a therapeutic strategy for targeting MYC-associated tumorigenesis and therapeutic resistance.Significance: This work identifies PDK1–PLK1–MYC signaling as a new oncogenic pathway driving oncogenic transformation and CSC self-renewal. Targeted inhibition of PDK1/PLK1 is robust in targeting MYC dependency in cancer cells. Thus, our findings provide important insights into cancer and CSC biology and have significant therapeutic implications. Cancer Discov; 3(10); 1156–71. ©2013 AACR.See related commentary by Cunningham and Ruggero, p. 1099This article is highlighted in the In This Issue feature, p. 1083Usage metrics
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