STRA6 promotes thyroid carcinoma progression via activation of the ILK/AKT/mTOR axis in cells and female nude mice

Background: Metastasis has emerged to be an important cause for poor
prognosis of thyroid carcinoma (TC) and its molecular mechanisms are not
fully understood. STRA6 is a multifunctional membrane protein widely
expressed in embryonic and adult tissues. The function and mechanism of
STRA6 in TC remain elusive. Objective: We aimed to explore the role of
STRA6 in TC progression and provide a therapeutic target for TC. Methods:
The expression and clinicopathological relevance of STRA6 were explored in
TC. Stable STRA6-knockdown TC cells were established and used to determine
the biological function of STRA6 in vitro and in vivo. RNA-sequencing and
Co-immunoprecipitation were performed to unveil the molecular mechanism of
STRA6 in TC progression. The potential of STRA6 as a therapeutic target
was evaluated by lipid nanoparticles (LNPs) containing siRNA. Results:
STRA6 was upregulated in TC and correlated with aggressive
clinicopathological features including extrathyroidal extension and lymph
node metastasis, which contributed to the poor prognosis of TC. STRA6
facilitated TC progression by enhancing proliferation and metastasis in
vitro and in vivo. Mechanistically, STRA6 could interact with ILK and
subsequently activate the AKT/mTOR signaling pathway. We further unveiled
that STRA6 reprogrammed lipid metabolism through SREBP1, which was crucial
for the metastasis of TC. Moreover, STRA6 siRNA delivered by LNP
significantly inhibited cell growth in xenograft tumor models.
Conclusions: Our study demonstrates the critical roles of STRA6
contributing to TC progression via the ILK/AKT/mTOR axis, which may
provide a novel prognostic marker as well as a promising therapeutic
target for aggressive TC.