2026-10-11T21:27:08Z https://api.figshare.com/v2/oai

oai:figshare.com:article/33940246 2026-09-18T17:58:24Z category_1 category_4 category_8 category_12 category_13 category_14 category_21 category_873 category_734 category_61 category_64 category_132 portal_5 item_type_3 month_year_09_2026

<p>siRNA smart pools used in this study.</p> Mona Nazemi (17797516) Bian Yanes (17797519) Eric Vancauwenberghe (15104560) Ifeoluwa Oyelade (25073602) Heather Walker (3014319) Elena Rainero (571002) Biophysics Biochemistry Microbiology Cell Biology Genetics Molecular Biology Biotechnology Chemical Sciences not elsewhere classified Biological Sciences not elsewhere classified Developmental Biology Cancer Infectious Diseases pancreatic cancer patients pancreatic cancer cells dependent s6 phosphorylation 2 &# 946 rapamycin complex 1 promotes &# 945 endure nutrient deficiency cancer cell survival lat1 &# 8722 fuelling mtorc1 signalling &# 945 1 integrin significant upregulation process ensures poor prognosis membrane localisation mammalian target limiting autophagy highly fibrotic glucose starvation findings highlight drug resistance driven pathway clinical relevance 4f2hc expression 3d models <div><p>Invasive breast and pancreatic cancer cells thrive within a collagen I-rich, poorly perfused extracellular matrix (ECM) network, necessitating robust metabolic adaptation to endure nutrient deficiency, such as glucose starvation. Here we demonstrate that collagen I is critical for the survival and growth of breast and pancreatic cancer cells. Mechanistically, collagen I promotes α2 β1 integrin-dependent S6 phosphorylation by the mammalian target of rapamycin complex 1 (mTORC1) and drives the membrane localisation of the LAT1−4F2hc amino acid transporter. This process ensures a sustained intracellular essential amino acid supply, further fuelling mTORC1 signalling and limiting autophagy. This collagen I-driven pathway is essential for cancer cell survival, as inhibiting the activity of α2 β1 integrin or the LAT1-4F2hc transporter significantly reduces cell growth and invasion in both 2D and 3D models. Finally, the clinical relevance of these transporters is underscored by the significant upregulation of LAT1-4F2hc expression in basal-like breast and pancreatic cancer patients, correlating with poor prognosis and drug resistance. Collectively, our findings highlight that targeting the LAT1−4F2hc transporter might represent a highly promising therapeutic strategy to limit cancer cell growth and invasion in highly fibrotic and nutrient-deprived tumours.</p></div> 2026-09-18T18:02:14Z Dataset Dataset 10.1371/journal.pbio.3003555.t001 https://figshare.com/articles/dataset/_p_siRNA_smart_pools_used_in_this_study_p_/33940246 CC BY 4.0