A Multifaceted Role for Myd88-Dependent Signaling in Progression of Murine Mammary Carcinoma.
Previous data obtained in our laboratory suggested that there may be constitutive signaling through the myeloid differentiation primary response gene 88 (Myd88)-dependent signaling cascade in murine mammary carcinoma. Here, we extended these findings by showing that, in the absence of an added Toll-like receptor (TLR) agonist, the myddosome complex was preformed in 4T1 tumor cells, and that Myd88 influenced cytoplasmic extracellular signal-regulated kinase (Erk)1/Erk2 levels, nuclear levels of nuclear factor-kappaB (NFκB) and signal transducer and activator of transcription 5 (STAT5), tumor-derived chemokine (C-C motif) ligand 2 (CCL2) expression, and in vitro and in vivo tumor growth. In addition, RNA-sequencing revealed that Myd88-dependent signaling enhanced the expression of genes that could contribute to breast cancer progression and genes previously associated with poor outcome for patients with breast cancer, in addition to suppressing the expression of genes capable of inhibiting breast cancer progression. Yet, Myd88-dependent signaling in tumor cells also suppressed expression of genes that could contribute to tumor progression. Collectively, these data revealed a multifaceted role for Myd88-dependent signaling in murine mammary carcinoma.
Department of Biology, Lafayette College, Easton, PA, USA.
Mary J
MJ
Higgins
Department of Biology, Lafayette College, Easton, PA, USA.
Antonio
A
Serrano
Department of Biology, Lafayette College, Easton, PA, USA.
Kofi Y
KY
Boateng
Department of Biology, Lafayette College, Easton, PA, USA.
Victoria A
VA
Parsons
Department of Biology, Lafayette College, Easton, PA, USA.
Tiffany
T
Phuong
Department of Biology, Lafayette College, Easton, PA, USA.
Alyssa
A
Seifert
Department of Biology, Lafayette College, Easton, PA, USA.
Jacob M
JM
Ricca
Department of Biology, Lafayette College, Easton, PA, USA.
Kyle C
KC
Tucker
Department of Biology, Lafayette College, Easton, PA, USA.
Alec S
AS
Eidelman
Department of Biology, Lafayette College, Easton, PA, USA.
Maureen A
MA
Carey
Department of Biology, Lafayette College, Easton, PA, USA.
Robert A
RA
Kurt
4T1; Myd88; NFκB; RNA-Seq; breast cancer