Differential AXL expression and Arf1 regulation control - stiffness-dependent Golgi organization in breast cancer cells

Sep 22, 2026

Integrin-mediated adhesion coordinates cellular survival and mechanotransduction, yet its impact on organelle organization during breast tumor progression remains unclear. Matrix stiffening accompanies cytoskeletal remodeling, but how it governs Golgi structure and function varies across cancer contexts. This study shows that in adherent MDA-MB-231 cells, increasing stiffness compacts and organizes the Golgi and boosts tubulin acetylation, whereas MCF7 cells retain a diffused Golgi. AXL localizes to the Golgi and, through Arf1 activation, forms a mechanosensitive AXL–Arf1–Golgi signaling axis controlling glycosylation and organelle organization under stiffness.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages16

Reading Time40 min

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Introduction

Breast cancer and matrix stiffness as mechanobiological cues

Integrin-mediated adhesion and Arf1-dependent Golgi regulation

Cancer-associated Golgi perturbations and open questions

© 2026 . Published by The Company of Biologists | Journal of Cell Science (2026) 139, jcs263956 . doi:10 . 1242/jcs.263956 RESEARCH ARTICLE Differential AXL expression and Arf1 regulation control stiffness-dependent Golgi organization in breast cancer cells Arnav Saha*, Tushar Sherkhane* and Nagaraj Balasubramanian‡ ABSTRACT | Integrin-mediated adhesion regulates cellular survival and mechanotransduction, processes often deregulated in cancers. During breast tumor progression, matrix stiffening influences cytoskeletal organization, although its effect on organelle organization and function remains unclear. Here, we examine how Golgi organization responds to matrix stiffness sensing in breast cancer cells. In adherent MDA-MB-231 cells, the Golgi becomes progressively more compact and organized with increasing matrix stiffness, accompanied by enhanced tubulin acetylation, indicating stiffness-dependent regulation. In contrast, MCF7 cells display a diffused or disorganized Golgi regardless of matrix stiffness. AXL, a receptor tyrosine kinase differentially expressed in MDA-MB-231 cells and absent in MCF7, localizes prominently to the Golgi. Inhibition or knockdown of AXL disrupted stiffness-dependent Golgi organization in MDA-MB-231 cells, whereas stable AXL expression in MCF7 restored Golgi organization at higher stiffness. A stiffness-dependent increase in AXL and Arf1 expression regulates Arf1 activation and localization to control mechanosensitive Golgi organization. Inhibition of AXL and/or Arf1 disrupted Golgi organization, tubulin acetylation and cell-surface glycosylation. Together, our findings reveal a mechanoresponsive AXL-Arf1-Golgi signaling axis that integrates matrix stiffness sensing with Golgi organization and function in breast cancer cells.
KEY WORDS: Adhesion, Mechanosensing, Matrix stiffness, Golgi organization, AXL, Arf1, Breast cancer | | --- | | INTRODUCTION
Breast cancer is the most common invasive cancer in women, affecting ∼12% of women worldwide (Shi et al., 2017) . Physical cues, such as increased matrix stiffness, solid stress and interstitial fluid pressure drive breast tumor progression (Chai et al., 2023) . Matrix stiffening is a key physical hallmark of breast cancer, which drives malignant transformation (Nia et al., 2020) . Average breast tissue stiffness ranges from 0.5 kPa to 2.5 kPa, whereas breast tumor tissue stiffness could vary from 4 kPa to beyond 20 kPa (Liu et al., 2021) .
Cells in their physiological niche can sense and respond to ECM mechanics, regulating migration, proliferation, differentiation and | | IISER Pune, Dr. Homi Bhabha Road, Pune 411008, India.
*These authors contributed equally to this work
‡Author for correspondence (nagaraj@i[iserpune.ac.in](iserpune.ac.in))
A.S. , 0009-0008-7801-4839; T.S. , 0009-0008-5207-4614; N. B. , 0000-0002- 8219-8844
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ([https://creativecommons.org/licenses/by/4.0](https://creativecommons.org/licenses/by/4.0)), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. | Handling Editor: Jennifer Lippincott-Schwartz Received 25 February 2025; Accepted 17 December 2025 spreading (Martino et al., 2018) . Mechanical cues are transmitted within cells, potentially influencing multiple pathways, includingthe dynamic organization of endomembrane organelles (Phuyalet al., 2020) . Sensing of mechanical cues by cells is primarily done by integrins (Ffrench-Constant, 2004), which regulate cellular mechanotransduction pathways (Berrier and Yamada, 2007) . Integrin-mediated cell–ECM adhesion governs key processes such as survival, growth and proliferation, and is frequently dysregulated in cancer (Schwartz, 1997) . Previous work from our laboratory has shown that integrin-mediated cell–matrix adhesion is vital in regulating Golgi organization an

FAQs

How does matrix stiffness affect Golgi organization in MDA-MB-231 versus MCF7 breast cancer cells?

In adherent MDA-MB-231 cells, Golgi organization becomes progressively more compact and organized with increasing matrix stiffness. In contrast, MCF7 cells show a diffused or disorganized Golgi regardless of matrix stiffness.

What role does AXL play in stiffness-dependent Golgi regulation?

AXL is differentially expressed in MDA-MB-231 cells and localized prominently to the Golgi. Inhibition or knockdown of AXL disrupts stiffness-dependent Golgi organization, while stable AXL expression in MCF7 restores Golgi organization at higher stiffness.

How do Arf1 and mechanotransduction connect to Golgi organization and function?

A stiffness-dependent increase in AXL and Arf1 regulates Arf1 activation and localization to control mechanosensitive Golgi organization. Inhibition of AXL and/or Arf1 disrupts Golgi organization, tubulin acetylation, and cell-surface glycosylation, indicating functional consequences.

Sep 22, 2026

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