title: Stress chaperone mortalin contributes to epithelial-mesenchymal transition and cancer metastasis.
abstract: Mortalin/mthsp70 (HSPA9) is a stress chaperone enriched in many cancers that has been implicated in carcinogenesis by promoting cell proliferation and survival. In the present study, we examined the clinical relevance of mortalin upregulation in carcinogenesis. Consistent with high mortalin expression in various human tumors and cell lines, we found that mortalin overexpression increased the migration and invasiveness of breast cancer cells. Expression analyses revealed that proteins involved in focal adhesion, PI3K-Akt and JAK-STAT signaling, all known to play key roles in cell migration and epithelial-to-mesenchymal transition (EMT), were upregulated in mortalin-expressing cancer cells. We further determined that expression levels of the mesenchymal markers vimentin (VIM), fibronectin (FN1), β-catenin (CTNNB1), CK14 (KRT14) and hnRNP-K were also increased upon mortalin overexpression, whereas the epithelial markers E-cadherin (CDH1), CK8 (KRT8), and CK18 (KRT18) were downregulated. Furthermore, shRNA-mediated and pharmacological inhibition of mortalin suppressed the migration and invasive capacity of cancer cells and was associated with a diminished EMT gene signature. Taken together, these findings support a role for mortalin in the induction of EMT, prompting further investigation of its therapeutic value in metastatic disease models.
authors.affiliation: Department of Bioengineering, Hanyang University.
authors.forename: Youjin
authors.initials: Y
authors.lastname: Na
authors.affiliation: Biomedical Research Institute, National Institute of Advanced Industrial Science & Technology (AIST).
authors.forename: Sunil C
authors.initials: SC
authors.lastname: Kaul
authors.affiliation: Biomedical Research Institute, National Institute of Advanced Industrial Science & Technology (AIST).
authors.forename: Jihoon
authors.initials: J
authors.lastname: Ryu
authors.affiliation: Department of Bioengineering, Hanyang University.
authors.forename: Jung-Sun
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Department of Bioengineering, Hanyang University.
authors.forename: Hyo Min
authors.initials: HM
authors.lastname: Ahn
authors.affiliation: Biomedical Research Institute, National Institute of Advanced Industrial Science & Technology (AIST).
authors.forename: Zeenia
authors.initials: Z
authors.lastname: Kaul
authors.affiliation: Biomedical Research Institute, National Institute of Advanced Industrial Science & Technology (AIST).
authors.forename: Rajkumar S
authors.initials: RS
authors.lastname: Kalra
authors.affiliation: Biomedical Research Institute, National Institute of Advanced Industrial Science & Technology (AIST).
authors.forename: Ling
authors.initials: L
authors.lastname: Li
authors.affiliation: Biomedical Research Institute, National Institute of Advanced Industrial Science & Technology (AIST), Central 4, 1-1-1 Higashi, Tsukuba, Ibaraki 305-8562, Japan.
authors.forename: Nashi
authors.initials: N
authors.lastname: Widodo
authors.affiliation: Department of Bioengineering, Hanyang University, South Korea.
authors.forename: Chae-Ok
authors.initials: CO
authors.lastname: Yun
authors.affiliation: Biomedical Research Institute, National Institute of Advanced Industrial Science & Technology (AIST), Central 4, 1-1-1 Higashi, Tsukuba, Ibaraki 305-8562, Japan renu-wadhwa@aist.go.jp.
authors.forename: Renu
authors.initials: R
authors.lastname: Wadhwa