S100A6 stimulates proliferation and migration of colorectal carcinoma cells through activation of the MAPK pathways

Abstract

The S100A6 protein, a member of the S100 protein family, is overexpressed in many tumors including colorectal carcinoma (CRC). Although recent studies showed that the elevated expression of S100A6 was associated with the stage and lymphatic permeation of CRC, little is known about whether and how S100A6 contributes to CRC development. Here we investigated the S100A6 expression in CRC tissues and cell lines, and explored the molecular mechanisms underlying the role of S100A6 in CRC development by examining cell proliferation and migration in vitro, and tumorigenicity in nude mice. The results show that S100A6 expression was markedly increased in CRC tissues and cell lines compared to normal colon tissues and a normal colon mucosal epithelial cell line, respectively. Recombinant adenovirus-mediated overexpression of S100A6 or treatment with recombinant S100A6 protein in HCT116, a CRC cell line with relative low S100A6 expression, resulted in enhanced cell proliferation and migration, and the mitogen-activated protein kinase (MAPK) activation in vitro, and tumor growth in vivo. Conversely, RNAi-mediated knockdown of S100A6 in LoVo, a CRC cell line with relative high S100A6 expression, resulted in reduced cell proliferation, migration and MAPK activity. S100A6-induced proliferation was partially attenuated by an ERK inhibitor while migration was suppressed by a p38 inhibitor. Taken together, our results suggest that the cellular effects of S100A6 are mediated by the ERK and p38 MAPK pathways, and modulation of these pathways may be employed for CRC prevention and therapy.

S100A6 promotes cell proliferation in human nasopharyngeal carcinoma via the p38/MAPK signaling pathway

“…This result confirms that p38/MAPK is a key signaling pathway by which S100A6 regulates the proliferation of NPC cells. This finding was different from an observation in colorectal carcinoma, in which S100A6 stimulated both p38 and ERK . The p38/MAPK signaling pathway is well known to play a critical role in the regulation of various cellular processes, and a growing body of evidence indicates the importance of p38/MAPK signaling in NPC progression.…”

Exosomes Derived from Human Primary and Metastatic Colorectal Cancer Cells Contribute to Functional Heterogeneity of Activated Fibroblasts by Reprogramming Their Proteome

“…Inspection of SS from neoHFFs treated with SW480‐Exos or SW620‐Exos revealed unique upregulation of protein S100‐A6 that is implicated in CAF and cancer cell proliferation and farnesyl‐diphosphate synthase (FDPS) that is implicated in proliferation . S100‐A6 belongs to the A group of the S100 protein family of calcium‐ binding proteins and is upregulated in tumor tissues including colon cancer tissues . Exogenous supplementation of S100‐A6 enhanced colon cancer cell proliferation in vitro and tumor growth in vivo through MAPK activation .…”

“…S100‐A6 belongs to the A group of the S100 protein family of calcium‐ binding proteins and is upregulated in tumor tissues including colon cancer tissues . Exogenous supplementation of S100‐A6 enhanced colon cancer cell proliferation in vitro and tumor growth in vivo through MAPK activation . FDPS is a key intermediate enzyme in the mevalonate pathway for lipid moieties synthesis that are critical for cell proliferation.…”

S100A11 promotes cell proliferation via P38/MAPK signaling pathway in intrahepatic cholangiocarcinoma

“…Previous studies indicated that S100 family can regulate tumor proliferation and metastasis via MAPK signaling pathway . In addition, S100A11 was reported to mediate tumor cell survival and malignant progression through activation of the P38 MAPK pathway .…”