Page 66 - D. Cancer biology

[D. Cancer biology-47]

Induction of HYOU1 via reciprocal crosstalk between NSCLC

cells and HUVECs control cancer progression and

chemoresistance in multicellular tumor spheroids

Minji Lee¹, Yeonhwa Song¹, Su-Yeon Lee¹, Sanghwa Kim¹, Inhee Choi², Jiho Kim³, Joo Hwan No⁴,

Se-Hyuk Kim¹, Haeng Ran Seo¹˙*

¹Cancer Biology Laboratory, Institut Pasteur Korea, Gyeonggi-do 13488, Korea, ²Medicinal Chemistry, Institut
Pasteur Korea, Gyeonggi-do 13488, Korea, ³Screening Discovery Platform, Institut Pasteur Korea, Gyeonggi-do

13488, Korea, ⁴Leishmania Research Laboratory, Institut Pasteur Korea, Gyeonggi-do 13488, Korea

Lung cancer ranks highest incidence and mortality in the world. The crosstalk between lung cancer cells and their

tumor microenvironment (TME) have begun to emerge as the “Achilles heel” of the disease. The most frequently
studied components of the TME is the endothelial cells (ECs). Our previous study showed that crosstalk between

lung cancer cells and ECs can elevate chemoresistance in multicellular tumor spheroids (MCTSs). In this study, we
revealed secreted factors by crosstalk between ECs and lung cancer can play pivotal roles in chemoresistance in

lung cancer spheroids. Subsequently, we identified HYOU1 (Hypoxia up-regulated protein 1) increased by secreted
factors from crosstalk between ECs and lung cancer in MCTSs. Direct interaction between ECs and lung cancer cells

also elevated expression of HYOU1 of lung cancer in MCTSs. Inhibition of HYOU1 expression effectively not only
suppresses stemness and malignancies, but also facilitates apoptosis and chemo sensitivity in lung cancer -MCTS.

The activation of AKT/ERK pathway was involved in the HYOU1-induced aggressive activity of lung cancer cells.
Together, our results demonstrated that HYOU1 could potentially be targeted to avoid the aggressive behavior of

cancer cells from crosstalk between EC and lung cancer on the TME.