The emerging role of microtubules in invasion plasticity

Abstract

The ability of cells to switch between different invasive modes during metastasis, also known as invasion plasticity, is an important characteristic of tumor cells that makes them able to resist treatment targeted to a particular invasion mode. Due to the rapid changes in cell morphology during the transition between mesenchymal and amoeboid invasion, it is evident that this process requires remodeling of the cytoskeleton. Although the role of the actin cytoskeleton in cell invasion and plasticity is already quite well described, the contribution of microtubules is not yet fully clarified. It is not easy to infer whether destabilization of microtubules leads to higher invasiveness or the opposite since the complex microtubular network acts differently in diverse invasive modes. While mesenchymal migration typically requires microtubules at the leading edge of migrating cells to stabilize protrusions and form adhesive structures, amoeboid invasion is possible even in the absence of long, stable microtubules, albeit there are also cases of amoeboid cells where microtubules contribute to effective migration. Moreover, complex crosstalk of microtubules with other cytoskeletal networks participates in invasion regulation. Altogether, microtubules play an important role in tumor cell plasticity and can be therefore targeted to affect not only cell proliferation but also invasive properties of migrating cells.

The Role of Galectin3, Tubulinβ, and Maspin in Promoting Tumor Budding in Colorectal Carcinoma and Their Clinical Implication

“…Tubulinβ expression in tumor cells in the tumor bulk, tumor buds, and stromal cells was observed, and its expression was associated with some adverse histopathological features such as high-grade tumors, lymph node metastasis, advanced stage, and TB. These results are in agreement with other studies, which discovered that tubulin expression in CRC and breast cancer was seen within tumor bulk, invasive front, and tumor buds and was associated with higher tumor grade, metastasis to lymph nodes, and worse prognosis 25–28 …”

“…These results are in agreement with other studies, which discovered that tubulin expression in CRC and breast cancer was seen within tumor bulk, invasive front, and tumor buds and was associated with higher tumor grade, metastasis to lymph nodes, and worse prognosis. [25][26][27][28] The previous results may point to the proposed role of tubulin in regulating tumor cell invasion, budding, and migration, which may be mediated by the induction of EMT, regulation of focal adhesion dynamics, and elongation of invadopodia. 29,30 In addition, maspin expression was recognized in most CRC cases included in this study and its nucleocytoplasmic expression was significantly associated with aggressive tumor features and poor prognosis and these results were in concordance with other studies that documented its poor prognostic role in colon, ovarian, and pancreatic cancers.…”

Molecular Insight into Gastric Cancer Invasion—Current Status and Future Directions

“…Remarkably, dual targeting of WNT5A and RhoA activity revealed a more efficient approach to inhibiting melanoma cell metastasis compared to the restoration of individual targets alone [ 212 ]. Increasing evidence has indicated that the biological properties of microtubules, an element of the cytoskeleton, and their dynamics are closely correlated with invasion plasticity [ 213 ]. Microtubule drugs hamper the invasion plasticity that regulates diverse efficiencies in each invasion mode.…”

“…Drugs blocking microtubule assembly induce the amoeboid invasion and subsequent RhoA activation. These findings imply that a combination of microtubule drugs, such as vincristine, and specific invasion inhibitors could synergistically target both the amoeboid and mesenchymal invasion [ 213 ].…”

Hepatitis B/C viruses upregulate TNNT1 expression to induce epithelial-mesenchymal transition and hepatocellular carcinogenesis via MTA2

“…5 The roles of TNNT1 actin cytoskeleton in cell invasion and plasticity are already well described. 6 TNNT1 is upregulated in immortalized retinal pigment epithelial cells and several tumor tissues, such as HCC, breast cancer, pancreatic cancer, and lung adenocarcinoma, and induces stem cells to obtain pluripotent characteristics. 7 However, the role and mechanism of TNNT1 during HCC development and hepatitis viruses-related HCC remain to be explored.…”