Overexpression of MICAL2, a novel tumor-promoting factor, accelerates tumor progression through regulating cell proliferation and EMT

Abstract

Molecule interacting with CasL 2 (MICAL2), a microtubule associated monooxygenase, is involved in cell growth, axon guidance, vesicle trafficking and apoptosis. Recent studies have demonstrated that MICAL2 is highly expressed in tumor and accelerates tumor progression and it is deemed to be a novel tumor-promoting factor. MICAL2 overexpression increases cell proliferation to accelerate tumor growth, and MICAL2 also promotes epithelial-mesenchymal transition (EMT)-related proteins to increase cancer cell metastasis. On mechanism, MICAL2 induces EMT by regulating SRF (serum response factor)/MRTF-A (myocardin related transcription factor A) signaling, Semaphorin/Plexin pathway and inducing ROS (Reactive oxygen species) production. In the present review, we introduced MICAL family, expatiated the structure and functions of MICALs, and summarized the mechanisms of MICAL2 involving tumor progression. The challenges and perspectives for MICAL2 in tumor are also discussed.

Keywords: MICAL2; cancer; epithelial-mesenchymal transition; metastasis..

Figure 1

A diagram of MICALs structure. MICAL1 is composed of monooxygenase (MO), calponinhomology (CH), LIM domain (LIM), and C-terminal domains (CTD). MICAL2 is composed of MO, CH, and LIM domains. MICAL3 is composed of MO, CH, LIM and CTD domains. MICAL-L1, 2 are composed of CH, LIM, and CTD domains.

Figure 2

Schemastic illustration of MICAL2 functions. MICAL2 induces F-actin depolymerization by redox modification. The depolymerization of F-actin reduces G-actin and accumulates MRTF-A through clustering. The accumulation of MRTF-A in nucleus actives SRF/MRTF-A-dependent gene transcription, and finally promotes cancer cells migration and invasion.

Figure 3

Schematic reprentation of MICAL2 as Sema platform. Sema interacts with plexin and activates plexin, and the activated plexin enhances MICAL2 monoxygenase activity and ROS intracellular concentration. MICAL2 accelerates F-actin depolymerization and increases cancer cell migration and invasion. ROS concentration induces EMT to promote migration and invasion.