Page 28 - D. Cancer biology

[D. Cancer biology-21]

Replenishing SOCS3 Suppresses Pancreatic Cancer

Progression

Sukyeong Jeong¹, Shinyoung Park¹, Jaehyeon Kim¹, Chohyun Kim¹, Mikyung Kim¹, Youngsil Choi¹,
Daewoong Jo¹˙*

¹Cellivery R&D Institute, Cellivery Therapeutics, Inc., Seoul 03929, South Korea

Suppressor of cytokine signaling 3 (SOCS3) is a negative regulator of Janus kinase/signal transducers and activators

of transcription (JAK/STAT) signaling, through which it plays pivotal roles in cancer progression. It suggests
therapeutic potential of intracellularly delivery SOCS3 recombinant protein to target tumors that depends on

JAK/STAT signaling for growth or survival. A cell-permeable SOCS3 protein with enhanced solubility, namely
improved cell-permeable (iCP)-SOCS3, is developed utilizing a sequence-optimized advanced macromolecule

transduction domain (aMTD) to deliver proteins into mammalian cells and tissues. iCP-SOCS3 increases apoptosis
by 67% and decreases cell viability, migration and invasion in PANC-1 pancreatic cancer cells by 95%, 84% and 68%,

respectively. iCP-SOCS3 is selectively toxic to tumor cells with deregulated JAK/STAT signaling, also suppressing the
growth of tumor xenografts and orthotropic pancreatic tumors (63-98%). These results provide further evidence

that SOCS3 can function as a tumor suppressor and establish intracellular SOCS3 delivery as a potential protein
therapy for pancreatic cancer by negatively regulating JAK/STAT signaling.