Mortalin contributes to colorectal cancer by promoting proliferation and epithelial–mesenchymal transition

Abstract

This study focused on the expression of mortalin in colorectal cancer (CRC). Mortalin activated the Wnt/β‐catenin pathway to accelerate cell proliferation and the epithelial–mesenchymal transition (EMT) program. Data from online databases displayed that the expression of mortalin was high in CRC, which was further validated using clinical specimens. Meanwhile, high mortalin expression was positively associated with a poor overall survival rate. Suppression of mortalin inhibited CRC cell proliferation as evaluated by the 3‐(4,5‐dimethyl‐2‐thiazolyl)‐2,5‐diphenyl‐2‐H‐tetrazolium bromide (MTT), colony formation, and immunofluorescence staining assays. In addition, depletion of mortalin inhibited CRC cell EMT progression and deactivated the Wnt/β‐catenin pathway. Altogether, mortalin is highly expressed in CRC and may indicate a poor prognosis. Mortalin accelerated CRC progression by stimulating cell proliferation and the EMT program. This study may provide a potential clinical therapeutic target for CRC.

Molecular Chaperones in Cancer Stem Cells: Determinants of Stemness and Potential Targets for Antitumor Therapy

“…Similarly, the elevated expression of GRP75 in intrahepatic cholangiocarcinoma cells was associated with EMT induction, which was accompanied by a decrease of the E-cadherin level while increasing the expression of vimentin and Snail; the suppression of GRP75 expression resulted in reverse effects, namely the accumulation of E-cadherin and downregulation of vimentin and Snail expression [253]. The EMT induction associated with GRP75-dependent activation of the Wnt/β-catenin signaling pathway was described for ovarian carcinoma [254] and colorectal cancer [255]. All these references [251][252][253][254][255] provide evidence that GRP75 does promote EMT in cancer cells, thus driving them to a stem (invasive and metastatic) phenotype.…”

“…The EMT induction associated with GRP75-dependent activation of the Wnt/β-catenin signaling pathway was described for ovarian carcinoma [254] and colorectal cancer [255]. All these references [251][252][253][254][255] provide evidence that GRP75 does promote EMT in cancer cells, thus driving them to a stem (invasive and metastatic) phenotype.…”

Sex Comb on Midleg Like-2 Accelerates Hepatocellular Carcinoma Cell Proliferation and Metastasis by Activating Wnt/β-Catenin/EMT Signaling

“… 27 28 In the EMT process, epithelial cells lose cell-to-cell adhesion and obtain properties of migration. 29 30 Corresponding to EMT characteristics, tumor cells overcome intercellular adhesion to gain invasiveness and motility, which is the first step in tumor progression. 31 32 It is well known that E-cadherin is a epithelial marker, while N-cadherin, Vimentin, and Snail are mesenchymal markers of EMT.…”

Ins and Outs of Heat Shock Proteins in Colorectal Carcinoma: Its Role in Carcinogenesis and Therapeutic Perspectives

“…HSP GRP78 mediates proper BRAFMT CRC cell proliferation and stability by regulating UPR [ 29 ]. Additionally, mortalin activates the Wnt/β-catenin pathway to promote cell proliferation and EMT transition in CRC cells [ 26 ]. A novel function of HSP70 has recently proved to be involved in CRC progression by activating oncogenic pathways such as the RTK signaling pathway.…”

“…This overexpression correlates with poor OS, invasion, and metastasis, and resistance to chemotherapy in CRC. The HSP70 member, mortalin, is associated with poor OS and may indicate an adverse prognosis for CRC patients [ 26 ]. Interestingly, according to recent studies, the Hsp70 family is the worst independent prognostic biomarker for primary CRC [ 27 ].…”