Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Aug;37(4):555-571.
doi: 10.1007/s10565-020-09574-w. Epub 2021 Jan 2.

S100A16 promotes metastasis and progression of pancreatic cancer through FGF19-mediated AKT and ERK1/2 pathways

Dan Fang #  1 , Chengfei Zhang #  1 , Ping Xu #  1 , Yinhua Liu #  2 , Xiao Mo  1 , Qi Sun  1 , Alaa Abdelatty  1   3 , Chao Hu  1 , Haojun Xu  1 , Guoren Zhou  4 , Hongping Xia  5   6   7   8 , Linhua Lan  9
Affiliations

S100A16 promotes metastasis and progression of pancreatic cancer through FGF19-mediated AKT and ERK1/2 pathways

Dan Fang et al. Cell Biol Toxicol. 2021 Aug.

Abstract

The S100 protein family genes play a crucial role in multiple stages of tumorigenesis and progression. Most of S100 genes are located at chromosome locus 1q21, which is a region frequently rearranged in cancers. Here, we examined the expression of the S100 family genes in paired pancreatic ductal adenocarcinoma (PDAC) samples and further validated the expression of S100A16 by immunohistochemistry staining. We found that S100A16 is significantly upregulated in clinical PDAC samples. However, its roles in PDAC are still unclear. We next demonstrated that S100A16 promotes PDAC cell proliferation, migration, invasion, and metastasis both in vitro and in vivo. Knockdown of S100A16 induces PDAC cell cycle arrest in the G2/M phase and apoptosis. Furthermore, we also demonstrated that S100A16 promotes PDAC cell proliferation, migration, and invasion via AKT and ERK1/2 signaling in a fibroblast growth factor 19 (FGF19)-dependent manner. Taken together, our results reveal that S100A16 is overexpressed in PDAC and promotes PDAC progression through FGF19-mediated AKT and ERK1/2 signaling, suggesting that S100A16 may be a promising therapeutic target for PDAC. S100A16 was upregulated in PDAC and associated with prognosis of PDAC patients. S100A16 regulates apoptosis and the cell cycle of pancreatic cancer cells. S100A16 promotes the progression of pancreatic cancer by AKT-ERK1/2 signaling. S100A16 may be a promising therapeutic target for PDAC.

Keywords: AKT; ERK1/2; Metastasis; Pancreatic cancer; S100A16.

PubMed Disclaimer

References

    1. Babini E, Bertini I, Borsi V, Calderone V, Hu X, Luchinat C, et al. Structural characterization of human S100A16, a low-affinity calcium binder. J Biol Inorg Chem: JBIC: a Publ Soc Biol Inorg Chem. 2011;16(2):243–56. https://doi.org/10.1007/s00775-010-0721-3 . - DOI
    1. Cao Z, Liao Q, Su M, Huang K, Jin J, Cao D. AKT and ERK dual inhibitors: the way forward? Cancer Lett. 2019;459:30–40. https://doi.org/10.1016/j.canlet.2019.05.025 . - DOI - PubMed
    1. Chen LL, Liang C. Aberrant S100A16 expression might be an independent prognostic indicator of unfavorable survival in non-small cell lung adenocarcinoma. PloS ONE. 2018;13(5):e0197402. https://doi.org/10.1371/journal.pone.0197402 . - DOI - PubMed - PMC
    1. Dhillon AS, Hagan S, Rath O, Kolch W. MAP kinase signalling pathways in cancer. Oncogene. 2007;26(22):3279–90. https://doi.org/10.1038/sj.onc.1210421 . - DOI - PubMed
    1. Ding L, Madamsetty VS, Kiers S, Alekhina O, Ugolkov A, Dube J et al. Glycogen synthase kinase-3 inhibition sensitizes pancreatic cancer cells to chemotherapy by abrogating the TopBP1/ATR-mediated DNA damage response. Clin Cancer Res. 2019;25(21):6452–62. https://doi.org/10.1158/1078-0432.CCR-19-0799 .

Publication types

MeSH terms

LinkOut - more resources