Cancer-Related Functions and Subcellular Localizations of Septins

Abstract

Since the initial discovery of septin family GTPases, the understanding of their molecular organization and cellular roles keeps being refined. Septins have been involved in many physiological processes and the misregulation of specific septin gene expression has been implicated in diverse human pathologies, including neurological disorders and cancer. In this minireview, we focus on the importance of the subunit composition and subcellular localization of septins relevant to tumor initiation, progression, and metastasis. We especially underline the importance of septin polymer composition and of their association with the plasma membrane, actin, or microtubules in cell functions involved in cancer and in resistance to cancer therapies. Through their scaffolding role, their function in membrane compartmentalization or through their protective function against protein degradation, septins also emerge as critical organizers of membrane-associated proteins and of signaling pathways implicated in cancer-associated angiogenesis, apoptosis, polarity, migration, proliferation, and in metastasis. Also, the question as to which of the free monomers, hetero-oligomers, or filaments is the functional form of mammalian septins is raised and the control over their spatial and temporal localization is discussed. The increasing amount of crosstalks identified between septins and cellular signaling mediators reinforces the exciting possibility that septins could be new targets in anti-cancer therapies or in therapeutic strategies to limit drug resistance.

Molecular Mechanisms Driving Cholangiocarcinoma Invasiveness: An Overview

“…They include, among others, Smad4, a common downstream effector of the TGF-β pathway 41 , septin 2 (SEPT2), a cytoskeletal protein controlling actin remodeling in cell migration 175 , platelet-activating factor acetylhydrolase 1b subunit 1 (PAFAH1B1) (also known as lissencephaly-1), a microtubule-associated protein shaping the cytoskeleton fibers 176 , neural cell adhesion molecule 1 (NCAM1), an adhesion molecule promoting the assembly of focal adhesions 177 , and FOXA1, an EMT-inducing transcription factor 15 . Of note, the ability of miR-122 and miR-200c to target RhoA and ZEB1/2, respectively, though well recognized in many cancer types, is not yet documented in CCA 178,179 .…”

14-3-3ε is a nuclear matrix protein, and its altered expression and localization are associated with curcumin-induced apoptosis of MG‑63 cells

“…Commonly, the cellular localization of proteins decides their functions ( 29 – 31 ). Using immunofluorescence labeling technology enabled the identified of the localization of 14-3-3ε in MG-63 cells and the nuclear matrix-intermediate filament system, prior to and following curcumin-induced apoptosis.…”

Cdc42EP5/BORG3 modulates SEPT9 to promote actomyosin function and melanoma invasion and metastasis

“…Septins are thought to form octameric 'rod-like' structures in the cytosol, and also associate into higher ordered cytoskeletal filaments in the cytoplasm or at the cell cortex 58,59 . Our findings demonstrate that in melanoma Cdc42EP5 is required for the assembly of septin structures at actomyosin bundles in 2D and 3D, possibly by enabling the recruitment of preassembled septin oligomers to actin structures 26 .…”

“…In vivo analyses confirm the importance of Cdc42EP5 for cancer cell motility and invasion, and reveal that Cdc42EP5 and SEPT9 are required for melanoma cells to metastasise. Given the emerging role of septins in cancer 59,68 , it will be interesting to investigate the relevance of septin networks in other types of cancers, as well as going in depth into their regulatory and effector mechanisms and any potential role of Borgs.…”