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Novel ER integral membrane protein SURF4 promotes

oncogenic transformation via ERK activation

Munju Kwon , Suyeon Woo , Jayoung Kim , Hee-Sun Choi , and Donjun Lee *
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1 Department of Convergence Medical Science, Pusan National University School of Medicine, Yangsan, 626-870

Abstract Result

SURF4 encodes for a conserved ER integral membrane

protein containing multiple putative transmembrane regions.

The recently described SURF4 protein was discovered

through in silico analysis of Kaplan-Meier survival curve from

pan-cancer patients. We found that by modulating SURF4 High SURF4 expression had significantly shorter overall

levels was affected in cellular transformation and cell survival than those with low expression

migration in vitro. In addition, SURF4 promotes oncogenic Kaplan-Meier survival curves for SURF4 were obtained using

transformation tools found at https://giantonline.org/#/app/dashboard. The

in vivo. Here, we further investigate the function of SURF4 survival curve relative to the median expression of SURF4 (high

and report that its activation promotes ERK activation in expression and low expression) in individuals affected by

prostate cells. These studies point to a novel molecular basis different cancer types (log-rank test).

for positive regulators of ERK activation signals in the solid

cancer cells.

Introduction

SURF4 regulates MEK-ERK Axis in 293T cells

Ras SURF4-overexpressing 293T cells were analyzed for ERK1/2,

Raf pERK1/2 (T202,Y204), JNK, pJNK (T183,Y185). MEK1/2,

pMEK1/2 (S217,S221), FOXO3A, p-FOXO3A (S294), AKT,

pAKT (S473,T308), mTOR, pmTOR (S2448), S6,

pS6 (S235/236), c-Myc and PP2A.

MEK

ERK

SURF4 ?

SURF4 interacts with MEK-ERK complexes in 293T cells

HEK293T cells transfected with vectors encoding either

HA-SURF4 or MYC-ERK2-MEK1 were lysed and subjected to

IP using an antibody directed against MYC.

Ras/Raf/MEK/ERK pathway in cancer cell

The Ras/Raf/MEK/ERK pathway is a crucial cell signaling

pathway utilized by eukaryotic cells for growth and

proliferation, and it is highly conserved amongst all

eukaryotic organisms. Mutations in this pathway lead to SURF4 directly binds ERK in 293T cells

uncontrolled growth and proliferation of cancerous cells. (A) HEK293T cells transfected with vectors encoding either

HA-SURF4 or FLAG-ERK were lysed and subjected to IP using

an antibody directed against HA.

(B) HEK293T cells transfected with vector encoding HA-SURF4

were lysed and subjected to IP using an antibody directed

against HA. SURF4 interacts with endogenous ERK

in 293T cells.

SURF4 overexpression

NIH3T3 cell subcutaneous injection

SURF4 regulates ERK activation in prostate cancer cells

SURF4-overexpressing PC3 cells were analyzed for ERK1/2,

pERK1/2 (T202,Y204), JNK, pJNK (T183,Y185). MEK1/2,

pMEK1/2 (S217,S221), FOXO3A, p-FOXO3A (S294), AKT

, pAKT (S473,T308), mTOR, pmTOR (S2448), S6

, pS6 (S235/236), c-Myc and PP2A.

Further Study

The oncogenic effect of SURF4 in NIH3T3 cells in vivo. ✓ The ER integral membrane protein, SURF4, interacts with ERK in 293T cells.

SURF4-overexpressing NIH3T3 cells were subcutaneously (sc) ✓ SURF4 regulates ERK activation in 293T and PC3 cells.

injected into a posterior flank of female nude mice.

Representative examples of tumor masses are shown. Error ✓ Based on these results, we will investigate the detail mechanism of interaction between SURF4 and ERK.

bars indicate the S.E.M. (**p < 0.01, *p < 0.05, n = 3–5).

✓ In addition, we will find the interaction among SURF4 and other signaling proteins.